bluuebunny/crossref_metadata_2025 huggingface dataset:
Minimal composite dynamics versus axion origin of the diphoton excess
Authors: Molinaro Emiliano , Sannino Francesco , Vignaroli Natascia
Published: July 2016

ATLAS and CMS observe deviations from the expected background in the diphoton invariant mass searches of new resonances around 750 GeV. We show that a simple realization in terms of a new pseudoscalar state can accommodate the observations. The model leads to further footprints that can be soon observed. The new state can be interpreted both as an axion or as a highly natural composite state arising from minimal models of dynamical electroweak (EW) symmetry breaking. We further show how to disentangle the two scenarios. Beyond the possible explanation of the diphoton excess, the results show that it is possible to directly test and constrain composite dynamics via processes stemming from its distinctive topological sector.
Remarks on graviton propagation in light of GW150914
Authors: Ellis John , Mavromatos Nick E. , Nanopoulos Dimitri V.
Published: July 2016

The observation of gravitational waves from the Laser Interferometer Gravitational-Wave Observatory (LIGO) event GW150914 may be used to constrain the possibility of Lorentz violation in graviton propagation, and the observation by the Fermi Gamma-Ray Burst Monitor (GBM) of a transient source in apparent coincidence may be used to constrain the difference between the velocities of light and gravitational waves: [Formula: see text].
A Digital-Based Low-Power Fully Differential Comparator
Authors: Singh Anil , Goel Ayushi , Agarwal Alpana
Published: July 2016

Low-power circuits are highly in demand in this power-hungry world of batteries and portable devices. Though many low-power techniques are prevalent at various stages of a VLSI design cycle, but most of them have retained their own domain. A novel, digital-in-concept, fully differential voltage comparator circuit has been implemented in this paper. This provides substantial reduction in the power consumption. It is highly cost-effective, both in terms of time and efforts as an analog circuit is being designed on digital basis. The proposed voltage comparator has been designed and simulated in Cadence[Formula: see text] Virtuoso Analog Design Environment using UMC 180[Formula: see text]nm CMOS technology at 1.8[Formula: see text]V supply.
Minimal hypersurfaces with small first eigenvalue in manifolds of positive Ricci curvature
Authors: Zhu Jonathan J.
Published: July 2016

In this paper we exhibit deformations of the hemisphere [Formula: see text], [Formula: see text], for which the ambient Ricci curvature lower bound [Formula: see text] and the minimality of the boundary are preserved, but the first Laplace eigenvalue of the boundary decreases. The existence of these metrics suggests that any resolution of Yau’s conjecture on the first eigenvalue of minimal hypersurfaces in spheres would likely need to consider more geometric data than a Ricci curvature lower bound.
The Farrell–Jones conjecture for hyperbolic and CAT(0)-groups revisited
Authors: Kasprowski Daniel , Rüping Henrik
Published: July 2016

We generalize the proof of the Farrell–Jones conjecture for CAT(0)-groups to a larger class of groups, for example also containing all groups that act properly and cocompactly on a finite product of hyperbolic graphs. In particular, this gives a unified proof of the Farrell–Jones conjecture for CAT(0)- and hyperbolic groups.
Development of an engineering bedrock map beneath Jakarta based on microtremor array measurements
Authors: Ridwan M. , Widiyantoro S. , Irsyam M. , Afnimar  , Yamanaka H.
Published: July 2016

Jakarta has been selected as a study area for seismic microzonation by considering its population and its infrastructure growth, seismicity and geological setting. One of the important factors in seismic hazard analysis is the characteristics of the ground overlying bedrock, and, as yet, this has not been studied for Jakarta. This study was intended to estimate the depth to bedrock by applying microtremor array exploration. The phase velocity of microtremors was estimated by the spatial autocorrelation (SPAC) method, whereas the S-wave velocity profile was estimated by inversion using a genetic algorithm. Microtremor array analysis has been conducted at 55 sites that covered the whole of Jakarta. The result of one-dimensional (1D) S-wave velocity profile estimation indicates that the engineering bedrock depth has pronounced differences between northern (>700 m) and southern Jakarta (about 300 m). A 3D S-wave velocity model was constructed from 1D profiles resulting from a second inversion in which the depth of constant-velocity layers, with velocities of 500, 700 and 900 m s
−1
, was determined. The constructed 3D velocity structures show a bedrock morphology that has a depth range of 350–725 m, with depths increasing towards northern Jakarta. The implication of differences in bedrock depth is that estimated seismic amplification for the thicker sediment will be higher.
Efficient and Flexible Deformation Representation for Data-Driven Surface Modeling
Authors: Gao Lin , Lai Yu-Kun , Liang Dun , Chen Shu-Yu , Xia Shihong
Published: July 2016

Effectively characterizing the behavior of deformable objects has wide applicability but remains challenging. We present a new rotation-invariant deformation representation and a novel reconstruction algorithm to accurately reconstruct the positions and local rotations simultaneously. Meshes can be very efficiently reconstructed from our representation by matrix pre-decomposition, while, at the same time, hard or soft constraints can be flexibly specified with only positions of handles needed. Our approach is thus particularly suitable for constrained deformations guided by examples, providing significant benefits over state-of-the-art methods. Based on this, we further propose novel data-driven approaches to mesh deformation and non-rigid registration of deformable objects. Both problems are formulated consistently as finding an optimized model in the shape space that satisfies boundary constraints, either specified by the user, or according to the scan. By effectively exploiting the knowledge in the shape space, our method produces realistic deformation results in real-time and produces high quality registrations from a template model to a single noisy scan captured using a low-quality depth camera, outperforming state-of-the-art methods.
Maximizing Performance Under a Power Cap
Authors: Zhang Huazhe , Hoffmann Henry
Published: July 2016

Power and thermal dissipation constrain multicore performance scaling. Modern processors are built such that they could sustain damaging levels of power dissipation, creating a need for systems that can implement processor power caps. A particular challenge is developing systems that can maximize performance within a power cap, and approaches have been proposed in both software and hardware. Software approaches are flexible, allowing multiple hardware resources to be coordinated for maximum performance, but software is slow, requiring a long time to converge to the power target. In contrast, hardware power capping quickly converges to the the power cap, but only manages voltage and frequency, limiting its potential performance. In this work we propose PUPiL, a hybrid software/hardware power capping system. Unlike previous approaches, PUPiL combines hardware's fast reaction time with software's flexibility. We implement PUPiL on real Linux/x86 platform and compare it to Intel's commercial hardware power capping system for both single and multi-application workloads. We find PUPiL provides the same reaction time as Intel's hardware with significantly higher performance. On average, PUPiL outperforms hardware by from 1:18-2:4 depending on workload and power target. Thus, PUPiL provides a promising way to enforce power caps with greater performance than current state-of-the-art hardware-only approaches.
ANVIL
Authors: Aweke Zelalem Birhanu , Yitbarek Salessawi Ferede , Qiao Rui , Das Reetuparna , Hicks Matthew , Oren Yossi , Austin Todd
Published: July 2016

Ensuring the integrity and security of the memory system is critical. Recent studies have shown serious security concerns due to "rowhammer" attacks, where repeated accesses to a row of memory cause bit flips in adjacent rows. Recent work by Google's Project Zero has shown how to leverage rowhammer-induced bit-flips as the basis for security exploits that include malicious code injection and memory privilege escalation. Being an important security concern, industry has attempted to defend against rowhammer attacks. Deployed defenses employ two strategies: (1) doubling the system DRAM refresh rate and (2) restricting access to the
CLFLUSH
instruction that attackers use to bypass the cache to increase memory access frequency (i.e., the rate of rowhammering). We demonstrate that such defenses are inadequte: we implement rowhammer attacks that both avoid using the
CLFLUSH
instruction and cause bit flips with a doubled refresh rate. Our next-generation
CLFLUSH-free
rowhammer attack bypasses the cache by manipulating cache replacement state to allow frequent misses out of the last-level cache to DRAM rows of our choosing.

To protect existing systems from more advanced rowhammer attacks, we develop a
software-based
defense, ANVIL, which thwarts all known rowhammer attacks on existing systems. ANVIL detects rowhammer attacks by tracking the locality of DRAM accesses using existing hardware performance counters. Our detector identifies the rows being frequently accessed (i.e., the aggressors), then selectively refreshes the nearby victim rows to prevent hammering. Experiments running on real hardware with the SPEC2006 benchmarks show that ANVIL has less than a 1% false positive rate and an average slowdown of 1%. ANVIL is low-cost and robust, and our experiments indicate that it is an effective approach for protecting existing and future systems from even advanced rowhammer attacks.
memif
Authors: Lin Felix Xiaozhu , Liu Xu
Published: July 2016

To harness a heterogeneous memory hierarchy, it is advantageous to integrate application knowledge in guiding frequent memory move, i.e., replicating or migrating virtual memory regions. To this end, we present memif, a protected OS service for asynchronous, hardware-accelerated memory move. Compared to the state of the art -- page migration in Linux, memif incurs low overhead and low latency; in order to do so, it not only redefines the semantics of kernel interface but also overhauls the underlying mechanisms, including request/completion management, race handling, and DMA engine configuration. We implement memif in Linux for a server-class system-on-chip that features heterogeneous memories. Compared to the current Linux page migration, memif reduces CPU usage by up to 15% for small pages and by up to 38x for large pages; in continuously serving requests, memif has no need for request batching and reduces latency by up to 63%. By crafting a small runtime atop memif, we improve the throughputs for a set of streaming workloads by up to 33%. Overall, memif has opened the door to software management of heterogeneous memory.
HIPStR
Authors: Venkat Ashish , Shamasunder Sriskanda , Shacham Hovav , Tullsen Dean M.
Published: July 2016

Heterogeneous Chip Multiprocessors have been shown to provide significant performance and energy efficiency gains over homogeneous designs. Recent research has expanded the dimensions of heterogeneity to include diverse Instruction Set Architectures, called Heterogeneous-ISA Chip Multiprocessors. This work leverages such an architecture to realize substantial new security benefits, and in particular, to thwart Return-Oriented Programming. This paper proposes a novel security defense called HIPStR -- Heterogeneous-ISA Program State Relocation -- that performs dynamic randomization of run-time program state, both within and across ISAs. This technique outperforms the state-of-the-art just-in-time code reuse (JIT-ROP) defense by an average of 15.6%, while simultaneously providing greater security guarantees against classic return-into-libc, ROP, JOP, brute force, JIT-ROP, and several evasive variants.
Programming Uncertain hings
Authors: McKinley Kathryn S.
Published: July 2016

Innovation flourishes with good abstractions. For instance, codification of the IEEE Floating Point standard in 1985 was critical to the subsequent success of scientific computing. Programming languages currently lack appropriate abstractions for uncertain data. Applications already use estimates from sensors, machine learning, big data, humans, and approximate algorithms, but most programming languages do not help developers address correctness, programmability, and optimization problems due to estimates.

To address these problems, we propose a new programming abstraction called Uncertain embedded into languages, such as C#, C++, Java, Python, and JavaScript. Applications use familiar discrete operations for estimates with Uncertain. Overloaded conditional operators specify hypothesis tests and applications use them to control false positives and negatives. A simple compositional operator expresses domain knowledge. We carefully restrict expressiveness such that we can build a runtime that implements correct statistical reasoning at conditionals. Our system relieves developers of the need to implement or deeply understand statistics. We demonstrate substantial programmability, correctness, and efficiency benefits of this programming model for GPS sensor navigation, approximate computing, machine learning, and xBox.

We encourage the community to develop and use abstractions for estimates.
Programmer Productivity in a World of Mushy Interfaces
Authors: Witchel Emmett
Published: July 2016

Since 1964, we had the notion that the instruction set architecture (ISA) is a useful and fairly opaque abstraction layer between hardware and software. Software rode hardware's performance wave while remaining gloriously oblivious to hardware's growing complexity. Unfortunately, the jig is up. We still have ISAs, but the abstraction no longer offers seamless portability---parallel software needs to be tuned for different core counts, and heterogeneous processing elements (CPUs, GPUs, accelerators) further complicate programmability. We are better at building large-scale heterogeneous processors than we are at programming them. Maintaining software across multiple current platforms is difficult and porting to future platforms is also difficult. There have been many technical responses: virtual ISAs (e.g., NVIDIA's PTX), higher-level programming interfaces (e.g., CUDA or OpenCL), and late-stage compilation and platform-specific tailoring (e.g., Android ART), etc.

A team of opinionated experts, drawn from the three ASPLOS communities will examine the problem of programmer productivity in the post-ISA world, first from the perspective of their area of expertise and then noting the contributions from the other two communities. What research will save us and how? This wide-ranging debate will frame important research areas for future work while being grounded in frank discussion about what has succeeded in the past. Attendees can expect actionable insight into important research issues as well an entertaining discussion.
Synopsis of the ASPLOS '16 Wild and Crazy Ideas (WACI) Invited-Speakers Session
Authors: Tsafrir Dan
Published: July 2016

The Wild and Crazy Ideas (WACI) session is a longstanding tradition at ASPLOS, soliciting talks that consist of forward-looking, visionary, inspiring, creative, far out or just plain amazing ideas presented in an exciting way. (Amusing elements in the presentations are tolerated ;-) but are in fact optional.)

The first WACI session took place in 1998. Back then, the call for talks included a problem statement, which contended that "papers usually do not get admitted to [such conferences as] ISCA or ASPLOS unless the systems that they describe are mature enough to run [some standard benchmark suites, which] has a chilling effect on the idea generation process---encouraging incremental research" [1]. The 1998 WACI session turned out to be a great success. Its webpage states that "there were 42 submissions [competing over] only eight time slots, [which resulted in] this session [having] a lower acceptance rate than the conference itself" [2].

But the times they are a-changin' [3], and the WACI session no longer enjoys that many submissions (Figure 1), perhaps because nowadays there exist many forums for researchers to describe/discuss their preliminary ideas, including: the ``hot topics in'' workshops [4--7]; a journal like CAL, dedicated to early results [8]; main conferences soliciting short submissions describing ``original or unconventional ideas at a preliminary stage'' in addition to regular papers [9]; and the many workshops co-located with main conferences, like ISCA '15, which hosted thirteen such workshops [10].

Regardless of the reason for the declining number of submissions, this time we've decided to organize the WACI session differently to ensure its continued high quality. Instead of soliciting talks via an open call and hoping for the best, we proactively invited speakers whom we believe are capable of delivering excellent WACI presentations. That is, this year's WACI session consists exclusively of invited speakers. Filling up the available slots turned out to be fairly easy, as most of the researchers we invited promptly accepted our invitation. The duration of each talk was set to be eight minutes (exactly as in the first WACI session from 1998) plus two minutes for questions.

The talks are outlined below. We believe they are interesting and exciting, and we hope the attendees of the session will find them stimulating and insightful.
Additional Parallel Features in Fortran
Authors: Long Bill
Published: July 2016

The next Fortran standard will include enhancements to the parallel programming model based on coarrays that is part of Fortran 2008. Included will be support for teams of images, synchronization using events, collective and atomic operations, enhanced error reporting, and continued execution after the failure of an image.
Bilateral Soleus H-Reflexes in Humans Elicited by Simultaneous Trains of Stimuli: Symmetry, Variability, and Covariance
Authors: Mezzarane Rinaldo A. , Kohn André F.
Published: July 2016

Experiments using electrical and mechanical activation of spinal reflexes have contributed important results toward the understanding of neuronal and synaptic dynamics involved in spinal neural circuits as well as their response to different inputs. In this work, data obtained from the simultaneous stimulation of both legs are analyzed to provide information on the degree of symmetry of the respective spinal reflex circuits and on the characteristics of reflex variability. H-reflexes recorded from relaxed muscles show a frequency-dependent amplitude depression when elicited by a train of stimuli. This effect has been attributed to homosynaptic depression. Soleus H-reflexes were recorded in response to trains of simultaneous stimuli applied to both legs in right-handed subjects that were sitting in a relaxed state. The first objective was to verify the existence of asymmetries in H-reflex parameters obtained from the two legs. We measured the mean, variance, and coefficient of variation of the depressed H-reflex amplitudes and the time constant of decay toward the depressed plateau. The second objective was the analysis of the time correlation of subsequent H-reflex amplitudes in a long train of responses recorded from a given leg. The statistical dependence of H-reflex amplitudes in the long trains recorded from both legs was also investigated. Data obtained from preliminary experiments showed that there was no effect of a given stimulus on the contralateral leg applied simultaneously or 1 s before, therefore validating the simultaneous stimulation paradigm. Paired t-tests indicated that several parameters measured bilaterally from soleus H-reflex trains of right-handed subjects were not statistically different in the overall, although individually there were statistically significant asymmetries, toward either the right or left leg. Sequences of H-reflex amplitudes, as measured by the auto-covariance, were either white or had a memory ranging from 2 up to 50 s. This indicates that the random fluctuations in presynaptic inhibition and/or postsynaptic inputs to motoneurons may have either fast or slow time courses. The average auto-covariance sequences of the right and left legs, computed from all subjects, were practically superposable. The cross-covariance between the bilateral H-reflex amplitudes showed a statistically significant peak at zero lag in some experiments, suggesting a correlation between the synaptic inputs to the Ia-motoneuron systems of the soleus muscles of both legs.
Computational Study on Monkey VOR Adaptation and Smooth Pursuit Based on the Parallel Control-Pathway Theory
Authors: Tabata Hiromitsu , Yamamoto Kenji , Kawato Mitsuo
Published: July 2016

Much controversy remains about the site of learning and memory for vestibuloocular reflex (VOR) adaptation in spite of numerous previous studies. One possible explanation for VOR adaptation is the flocculus hypothesis, which assumes that this adaptation is caused by synaptic plasticity in the cerebellar cortex. Another hypothesis is the model proposed by Lisberger that assumes that the learning that occurs in both the cerebellar cortex and the vestibular nucleus is necessary for VOR adaptation. Lisberger's model is characterized by a strong positive feedback loop carrying eye velocity information from the vestibular nucleus to the cerebellar cortex. This structure contributes to the maintenance of a smooth pursuit driving command with zero retinal slip during the steady-state phase of smooth pursuit with gain 1 or during the target blink condition. Here, we propose an alternative hypothesis that suggests that the pursuit driving command is maintained in the medial superior temporal (MST) area based on MST firing data during target blink and during ocular following blank, and as a consequence, we assume a much smaller gain for the positive feedback from the vestibular nucleus to the cerebellar cortex. This hypothesis is equivalent to assuming that there are two parallel neural pathways for controlling VOR and smooth pursuit: a main pathway of the semicircular canals to the vestibular nucleus for VOR, and a main pathway of the MST—dorsolateral pontine nuclei (DLPN)—flocculus/ventral paraflocculus to the vestibular nucleus for smooth pursuit. First, we theoretically demonstrate that this parallel control-pathway theory can reproduce the various firing patterns of horizontal gaze velocity Purkinje cells in the flocculus/ventral paraflocculus dependent on VOR in the dark, smooth pursuit, and VOR cancellation as reported in Miles et al. at least equally as well as the gaze velocity theory, which is the basic framework of Lisberger's model. Second, computer simulations based on our hypothesis can stably reproduce neural firing data as well as behavioral data obtained in smooth pursuit, VOR cancellation, and VOR adaptation, even if only plasticity in the cerebellar cortex is assumed. Furthermore, our computer simulation model can reproduce VOR adaptation automatically based on a heterosynaptic interaction model between parallel fiber inputs and climbing fiber inputs. Our results indicate that different assumptions about the site of pursuit driving command maintenance computationally lead to different conclusions about where the learning for VOR adaptation occurs. Finally, we propose behavioral and physiological experiments capable of discriminating between these two possibilities for the site of pursuit driving command maintenance and hence for the sites of learning and memory for VOR adaptation.
Encoding of Compressive Stress During Indentation by Slowly Adapting Type I Mechanoreceptors in Rat Hairy Skin
Authors: Ge Weiqing , Khalsa Partap S.
Published: July 2016

The mechanical state encoded by slowly adapting type 1 mechanoreceptors (SAI) during indentation was examined using an isolated preparation in a rat model. Skin and its intact innervation were harvested from the medial thigh of the rat hindlimb and placed in a dish, with the corium side down, containing synthetic interstitial fluid. The margins of the skin were coupled to an apparatus that could stretch and apply compression to the skin. Using a standard teased nerve preparation, the neural responses of single SAIs were identified. SAIs were stimulated, using controlled compressive stress while simultaneously measuring displacement, by compressing the skin between indenters (flat cylinders) of different diameters and a hard platform. SAIs were subcategorized according to whether their neural response saturated above or below 10 kPa compressive stress (SAI-H or SAI-L, respectively). Linear regression was used to evaluate the relationships between neuron response and stress and force and displacement. For all SAIs, the mean neural response was significantly and substantially more highly correlated with compressive stress than force or displacement. For the SAI-L subcategory, the mean correlation coefficient was significantly and substantially greater for stress than for force but not significantly different for displacement. The data from this study support the hypothesis that SAI mechanoreceptors stimulated by indentation encode compressive stress rather than force, displacement, or strain.
Ca2+-Dependent Ca2+Clearance Via Mitochondrial Uptake and Plasmalemmal Extrusion in Frog Motor Nerve Terminals
Authors: Suzuki S. , Osanai M. , Mitsumoto N. , Akita T. , Narita K. , Kijima H. , Kuba K.
Published: July 2016

Ca2+clearance in frog motor nerve terminals was studied by fluorometry of Ca2+indicators. Rises in intracellular Ca2+([Ca2+]i) in nerve terminals induced by tetanic nerve stimulation (100 Hz, 100 or 200 stimuli: Ca2+transient) reached a peak or plateau within 6–20 stimuli and decayed at least in three phases with the time constants of 82–87 ms (81–85%), a few seconds (11–12%), and several tens of seconds (less than a few percentage). Blocking both Na/Ca exchangers and Ca2+pumps at the cell membrane by external Li+and high external pH (9.0), respectively, increased the time constants of the initial and second decay components with no change in their magnitudes. By contrast, similar effects by Li+alone, but not by high alkaline alone, were seen only on 200 stimuli-induced Ca2+transients. Blocking Ca2+pumps at Ca2+stores by thapsigargin did not affect 100 stimuli-induced Ca2+transients but increased the initial decay time constant of 200 stimuli-induced Ca2+transients with no change in other parameters. Inhibiting mitochondrial Ca2+uptake by carbonyl cyanide m-chlorophenylhydrazone markedly increased the initial and second decay time constants of 100 stimuli-induced Ca2+transients and the amplitudes of the second and the slowest components. Plotting the slopes of the decay of 100 stimuli-induced Ca2+transients against [Ca2+]iyielded the supralinear [Ca2+]idependence of Ca2+efflux out of the cytosol. Blocking Ca2+extrusion or mitochondrial Ca2+uptake significantly reduced this [Ca2+]i-dependent Ca2+efflux. Thus Ca2+-dependent mitochondrial Ca2+uptake and plasmalemmal Ca2+extrusion clear out a small Ca2+load in frog motor nerve terminals, while thapsigargin-sensitive Ca2+pump boosts the clearance of a heavy Ca2+load. Furthermore, the activity of plasmalemmal Ca2+pump and Na/Ca exchanger is complementary to each other with the slight predominance of the latter.
Directional Asymmetry of Neurons in Cortical Areas MT and MST Projecting to the NOT-DTN in Macaques
Authors: Hoffmann K.-P. , Bremmer F. , Thiele A. , Distler C.
Published: July 2016

The cortical projection to the subcortical pathway underlying the optokinetic reflex was studied using antidromic electrical stimulation in the midbrain structures nucleus of the optic tract and dorsal terminal nucleus of the accessory optic system (NOT-DTN) while simultaneously recording from cortical neurons in the superior temporal sulcus (STS) of macaque monkeys. Projection neurons were found in all subregions of the middle temporal area (MT) as well as in the medial superior temporal area (MST). Antidromic latencies ranged from 0.9 to 6 ms with a median of 1.8 ms. There was a strong bias in the population of cortical neurons projecting to the NOT-DTN for ipsiversive stimulus movement (towards the recording side), whereas in the population of cortical neurons not projecting to the NOT-DTN a more or less equal distribution of stimulus directions was evident. Our data indicate that there is no special area in the posterior STS coding for ipsiversive horizontal stimulus movement. Instead, a specific selection of cortical neurons from areas MT and MST forms the projection to the NOT-DTN and as a subpopulation has the same directional bias as their subcortical target neurons. These findings are discussed in relation to the functional grouping of cortical output as an organizational principle for specific motor responses.
Sensitization to Mechanical Stimulation by Inflammatory Mediators and by Mild Burn in Canine Visceral Nociceptors In Vitro
Authors: Koda Hisashi , Mizumura Kazue
Published: July 2016

Hyperalgesia to mechanical stimulation and heat is commonly observed in inflamed conditions. Although sensitization to heat is well documented and its mechanism has also been well studied, it remains unclear whether and how nociceptors are sensitized to mechanical stimulation. Therefore we conducted in vitro investigation of which inflammatory mediators (bradykinin, histamine, prostaglandin E2, and protons) sensitize nociceptors to suprathreshold mechanical stimulation and at what concentrations. In addition, we studied the effects of possible second messengers for these mediators downstream of the receptors and also the effects of mild burn. Single polymodal receptor activities were recorded in canine testis-spermatic nerve preparations excised from deeply anesthetized dogs. Mechanical stimulation was applied to the identified receptive field for 10 s with a servo-controlled mechanical stimulator. Bradykinin at 0.001 μM induced neither excitation nor facilitation of the mechanical response; however, it facilitated the mechanical response at 0.01 μM and higher, levels at which significant excitation was also induced by bradykinin alone. Histamine excited the nociceptor and sensitized it to mechanical stimulation at 10 μM and higher. PG E2also sensitized the mechanical response, but starting at 1 μM, without inducing excitation by itself. The effects of two possible intracellular messengers for these mediators were studied using forskolin (10 μM), which increases intracellular cAMP, and a protein-kinase-C-stimulating phorbol ester, phorbol 12,13-dibutyrate (0.1 μM). Both substances reversibly facilitated the mechanical response of testicular polymodal receptors. In contrast, low-pH solution (pH: 6.6–4.5) seldom induced excitation and failed to facilitate the mechanical response. After 55°C, 30-s heat stimulation, testicular polymodal receptors were sensitized to mechanical stimulation. These results demonstrated that inflammatory mediators and burn sensitized nociceptor responses to mechanical stimulation and provide support for the idea that peripheral nociceptor sensitization is a mechanism involved in hyperalgesia to mechanical stimulation in inflamed tissues.
NMDA Receptor-Mediated Currents in Rat Cerebellar Granule and Unipolar Brush Cells
Authors: Billups Daniela , Liu Ying-Bing , Birnstiel Susanne , Slater N. Traverse
Published: July 2016

The properties of N-methyl-d-aspartate (NMDA) receptor-mediated currents at the giant cerebellar mossy-fiber unipolar brush cell (UBC) synapse were compared with those of adjacent granule cells using patch-clamp recording methods in thin slices of rat cerebellar nodulus. In UBCs, NMDA receptor-mediated excitatory postsynaptic currents (EPSCs) decayed as a single exponential whose time constant was independent of membrane potential. The EPSC was reduced in all cells by the NR1/NR2B-selective antagonist ifenprodil, and the Zn2+ chelator N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) produced a transient potentiation in 50% of cells. In contrast, the NMDA EPSC in granule cells decayed as a double exponential that dramatically switched to a slower rate at positive membrane potentials. The synaptic response in some granule cells also displayed a late second peak at positive potentials, and in others, activation of mossy fibers produced repetitive trains of EPSCs indicating they may be postsynaptic to the UBC network. Single-channel recordings of outside-out somatic patches from UBCs in magnesium-free solution revealed only high-conductance (50 pS) channels whose open time was increased with depolarization, but the opening frequency was decreased to yield a low ( p o = 0.0298), voltage-independent opening probability. Lowering extracellular calcium (2.5–0.25 mM) had no effects on channel gating, although an increase of single-channel conductance was observed at lower calcium concentrations. Taken together, the data support the notion that the NMDA receptor in UBCs may comprise both NR1/NR2A and NR1/NR2B receptors. Furthermore, the properties of the EPSC in these two classes of feedforward glutamatergic interneurons display fundamental differences that may relate to their roles in synaptic integration.
Neuromodulatory Role of Serotonin in the Ferret Thalamus
Authors: Monckton James E. , McCormick David A.
Published: July 2016

Serotonergic fibers broadly innervate the thalamus and may influence the sleep wake cycle, attention, and other processes through modulation of neurons in this structure. However, the actions of serotonin in the dorsal thalamus have been investigated in detail only in the dorsal lateral geniculate nucleus. In the present study, we examined the action of serotonin in several different regions of the ferret dorsal thalamus, including the associative nuclei, using the in vitro slice preparation and intracellular recording techniques. In nearly all nuclei examined, the predominant action of serotonin was one of hyperpolarization and inhibition of the tonic firing mode. The magnitude of the hyperpolarizing response decreased with age and varied greatly across and somewhat within nuclei maintaining the following relationship (in descending order of magnitude): lateral posterior, lateral dorsal, pulvinar, mediodorsal, center median, anteroventral, central lateral, ventral basal, and medial geniculate. This hyperpolarization is elicited through two mechanisms: one direct and the other via local interneurons. The direct action occurs through an increase in potassium conductance mediated through the 5-HT1A receptor. This conclusion is supported by the findings that it persists in the presence of tetrodotoxin and block of GABAergic synaptic transmission, the reversal potential shifts in a Nernstian fashion with changes in extracellular potassium concentration, and the response is antagonized by the 5-HT1A antagonist WAY100635 and mimicked by the application of the 5-HT1A–selective agonist 8-OH DPAT. The second mechanism by which 5-HT evoked a hyperpolarization was through the activation of local interneurons. In slices in which GABA receptors were not blocked, 5-HT application increased the frequency and amplitude of spontaneous inhibitory postsynaptic potentials (IPSPs) occurring in thalamocortical neurons. Application of 5-HT to physiologically or morphologically identified interneurons evoked a prolonged suprathreshold depolarization. Our results suggest that serotonergic inputs act differentially across the thalamus in a complex manner involving direct and indirect mechanisms. It appears that 5-HT has a greater direct postsynaptic inhibitory influence in the posterior, medial, and intralaminar nuclei than in the primary sensory nuclei.
Dissociated Retinal Neurons Form Periodically Active Synaptic Circuits
Authors: Harris Richard E. , Coulombe Margaret G. , Feller Marla B.
Published: July 2016

Throughout the developing nervous system, immature circuits generate rhythmic activity patterns that influence the formation of adult networks. The cellular mechanisms underlying this spontaneous, correlated activity can be studied in dissociated neuronal cultures. Using calcium imaging and whole cell recording, we showed that cultured dissociated mammalian retinal neurons form networks that produce spontaneous, correlated, highly periodic activity. As the culture matures, the spatial correlations of the periodic calcium transients evolve from being highly synchronized across neighboring cells to propagating across the culture in a wavelike manner reminiscent of retinal waves recorded in vivo. Spontaneous calcium transients and synaptic currents were blocked either by cadmium, tetrodotoxin, or the glutamate receptor antagonist 6,7-dinitroquinoxaline, indicating that the periodic activity was driven primarily by synaptic transmission between retinal ganglion cells. Evoked responses between pairs of ganglion cells exhibited paired-pulse synaptic depression, and the time constant of recovery from this depression was similar to the interval between periodic events. These results suggest that synaptic depression may regulate the frequency of network activity. Together, these findings provide insight into how networks containing primarily excitatory connections generate highly correlated activity.
Transient Analgesia Evoked by Noxious Stimulus Offset
Authors: Grill Joshua D. , Coghill Robert C.
Published: July 2016

Pain has long been thought to wax and wane in relative proportion to fluctuations in the intensity of noxious stimuli. Dynamic aspects of nociceptive processing, however, remain poorly characterized. Here we show that small decreases (±1–3°C) in noxious stimulus temperatures (47–50°C) evoked changes in perceived pain intensity that were as much as 271% greater than those of equal magnitude increases. These decreases in perceived pain intensity were sufficiently large to be indistinguishable from those evoked by 15°C decreases to clearly innocuous levels. Furthermore, decreases in pain ratings following noxious stimulus offset were significantly greater than those occurring during adaptation to constant temperature stimuli. Together, these findings indicate that an analgesic mechanism is activated during noxious stimulus offset. This analgesic phenomenon may serve as a temporal contrast enhancement mechanism to amplify awareness of stimulus offset and to reinforce escape behaviors. Disruption of this mechanism may contribute importantly to chronic pain.
Differential Modulation of Nucleus Accumbens Synapses
Authors: Brundege James M. , Williams John T.
Published: July 2016

The nucleus accumbens (NAcc) is a brain region involved in functions ranging from motivation and reward to feeding and drug addiction. The NAcc is typically divided into two major subdivisions, the shell and the core. The primary output neurons of both of these areas are medium spiny neurons (MSNs), which are quiescent at rest and depend on the relative input of excitatory and inhibitory synapses to determine when they fire action potentials. These synaptic inputs are, in turn, regulated by a number of neurochemical signaling agents that can ultimately influence information processing in the NAcc. The present study characterized the ability of three major signaling pathways to modulate synaptic transmission in NAcc MSNs and compared this modulation across different synapses within the NAcc. The opioid [Met]5enkephalin (ME) inhibited excitatory postsynaptic currents (EPSCs) in shell MSNs, an effect mediated primarily by μ-opioid receptors. Forskolin, an activator of adenylyl cyclase, potentiated shell EPSCs. An analysis of miniature EPSCs indicated a primarily presynaptic site of action, although a smaller postsynaptic effect may have also contributed to the potentiation. Adenosine and an adenosine A1-receptor agonist inhibited shell EPSCs, although no significant tonic inhibition by endogenous adenosine was detected. The effects of these signaling agents were then compared across four different synapses in the NAcc: glutamatergic EPSCs and GABAergic inhibitory postsynaptic currents (IPSCs) in both the core and shell subregions. ME inhibited all four of these synapses but produced a significantly greater inhibition of shell IPSCs than the other synapses. Forskolin produced an increase in transmission at each of the synapses tested. However, analysis of miniature IPSCs in the shell showed no sign of a postsynaptic contribution to this potentiation, in contrast to the shell miniature EPSCs. Tonic inhibition of synaptic currents by endogenous adenosine, which was not observed in shell EPSCs, was clearly present at the other three synapses tested. These results indicate that neuromodulation can vary between the different subregions of the NAcc and between the different synapses within each subregion. This may reflect differences in neuronal interconnections and functional roles between subregions and may contribute to the effects of drugs acting on these systems.
Nigrostriatal Lesion and Dopamine Agonists Affect Firing Patterns of Rodent Entopeduncular Nucleus Neurons
Authors: Ruskin David N. , Bergstrom Debra A. , Walters Judith R.
Published: July 2016

Altered activity of the entopeduncular nucleus, the rodent homologue of the globus pallidus internal segment in primates, is thought to mediate behavioral consequences of midbrain dopamine depletion in rodents. Few studies, however, have examined dopaminergic modulation of spiking activity in this nucleus. This study characterizes changes in entopeduncular neuronal activity after nigrostriatal dopaminergic lesion and the effects of systemic treatment with selective D1(SKF 38393) and D2 (quinpirole) agonists in lesioned rats. Extracellular single-unit recordings were performed in awake immobilized rats, either in neurologically intact animals ( n = 42) or in animals that had received unilateral 6-hydroxydopamine infusion into the medial forebrain bundle several weeks previously ( n = 35). Nigrostriatal lesion altered baseline activity of entopeduncular neurons in several ways. Interspike interval distributions had significantly decreased modes and significantly increased coefficient of variation, skewness and kurtosis; yet interspike interval mean (the inverse of firing rate) was not affected. Also, spectral analysis of autocorrelograms indicated that lesion significantly reduced the incidence of regular-spiking neurons and increased the incidence of neurons with 4–18 Hz oscillations. Dopamine agonist treatment reversed some lesion-induced effects: quinpirole reversed changes in interspike interval distribution mode and coefficient of variation, while combined quinpirole and SKF 38393 blocked the appearance of 4–18 Hz oscillations. However, no agonist treatment normalized all aspects of entopeduncular activity. Additionally, inhibition of firing rates by D1 or combined D1/D2 receptor activation indicated that dopamine agonists affected the overall level of entopeduncular activity in a manner similar to that found in the substantia nigra pars reticulata and globus pallidus internal segment after dopamine neuron lesion. These data demonstrate that lesion of the nigrostriatal tract leads to modifications of several aspects of firing pattern in the rodent entopeduncular nucleus and so expand on similar findings in the rodent substantia nigra pars reticulata and in the globus pallidus internal segment in humans and nonhuman primates. The results support the view that dysfunction in the basal ganglia after midbrain dopamine neuron loss relates more consistently to abnormal activity patterns than to net changes in firing rate in the basal ganglia output nuclei, while overall decreases in firing rate in these structures may play a more important role in adverse motor reactions to dopamine agonist treatments.
Constraints on the Source of Short-Term Motion Adaptation in Macaque Area MT. I. The Role of Input and Intrinsic Mechanisms
Authors: Priebe Nicholas J. , Churchland Mark M. , Lisberger Stephen G.
Published: July 2016

Neurons in area MT, a motion-sensitive area of extrastriate cortex, respond to a step of target velocity with a transient-sustained firing pattern. The transition from a high initial firing rate to a lower sustained rate occurs over a time course of 20–80 ms and is considered a form of short-term adaptation. The present paper asks whether adaptation is due to input-specific mechanisms such as short-term synaptic depression or if it results from intrinsic cellular mechanisms such as spike-rate adaptation. We assessed the contribution of input-specific mechanisms by using a condition/test paradigm to measure the spatial scale of adaptation. Conditioning and test stimuli were placed within MT receptive fields but were spatially segregated so that the two stimuli would activate different populations of inputs from the primary visual cortex (V1). Conditioning motion at one visual location caused a reduction of the transient firing to subsequent test motion at a second location. The adaptation field, estimated as the region of visual space where conditioning motion caused adaptation, was always larger than the MT receptive field. Use of the same stimulus configuration while recording from direction-selective neurons in V1 failed to demonstrate either adaptation or the transient-sustained response pattern that is the signature of short-term adaptation in MT. We conclude that the shift from transient to sustained firing in MT cells does not result from an input-specific mechanism applied to inputs from V1 because it operates over a wider range of the visual field than is covered by receptive fields of V1 neurons. We used a direct analysis of MT neuron spike trains for many repetitions of the same motion stimulus to assess the contribution to adaptation of intrinsic cellular mechanisms related to spiking. On a trial-by-trial basis, there was no correlation between number of spikes in the transient interval and the interval immediately after the transient period. This is opposite the prediction that there should be a correlation if spikes cause adaptation directly. Further, the transient was suppressed or extinguished, not delayed, in trials in which the neuron emitted zero spikes during the interval that showed a transient in average firing rate. We conclude that the transition from transient to sustained firing in neurons in area MT is caused by mechanisms that are neither input-specific nor controlled by the spiking of the adapting neuron. We propose that the short-term adaptation observed in area MT emerges from the intracortical circuit within MT.
Analysis of Random Variation in Subthreshold FGMOSFET
Authors: Banchuin Rawid
Published: July 2016

The analysis of random variation in the performance of Floating Gate Metal Oxide Semiconductor Field Effect Transistor (FGMOSFET) which is an often cited semiconductor based electronic device, operated in the subthreshold region defined in terms of its drain current (ID), has been proposed in this research.IDis of interest because it is directly measurable and can be the basis for determining the others. All related manufacturing process induced device level random variations, their statistical correlations, and low voltage/low power operating condition have been taken into account. The analysis result has been found to be very accurate since it can fit the nanometer level SPICE BSIM4 based reference with very high accuracy. By using such result, the strategies for minimizing variation inIDcan be found and the analysis of variation in the circuit level parameter of any subthreshold FGMOSFET based circuit can be performed. So, the result of this research has been found to be beneficial to the variability aware design of subthreshold FGMOSFET based circuit.