ABSTRACT Brain-machine interfaces have shown promise in extracting upper extremity movement intention from the thoughts of nonhuman primates and people with tetraplegia. Attempts to restore a user’s own hand and arm function have employed functional electrical stimulation (FES), but most work has restored discrete grasps. Little is known about how well FES can control continuous finger movements. Here, we use a low-power brain-controlled functional electrical stimulation (BCFES) system to restore continuous volitional control of finger positions to a monkey with a temporarily paralyzed hand. In a one-dimensional, continuous, finger-related target acquisition task, the monkey improved his success rate to 83% (1.5s median acquisition time) when using the BCFES system during temporary paralysis from 8.8% (9.5s median acquisition, equivalent to chance) when attempting to use his temporarily paralyzed hand. With two monkeys under general anesthesia, we found FES alone could control the monkeys’ fingers to rapidly reach targets in a median 1.1s but caused oscillation about the target. Finally, when attempting to perform a virtual two-finger continuous target acquisition task in brain-control mode following temporary hand paralysis, we found performance could be completely recovered by executing recalibrated feedback-intention training one time following temporary paralysis. These results suggest that BCFES can restore continuous finger function during temporary paralysis using existing low-power technologies and brain-control may not be the limiting performance factor in a BCFES neuroprosthesis.
Low-grade gliomas represent the most frequent primary brain tumors in children, and are also an important category of brain neoplasms in young adults. They are characterized by slow growth, but often associated with increased morbidity, as well as mortality in the subset that develop histologic progression. Pathologically they correspond to WHO grade I or II and include pilocytic astrocytoma (PA), pilomyxoid astrocytoma variant, angiocentric glioma, diffuse astrocytoma, oligodendroglioma, oligoastrocytoma, and pleomorphic xanthoastrocytoma (PXA). Although all low-grade glioma subtypes may develop in children and adults, and be histologically indistinguishable in these two populations, there are important clinical and molecular differences. As a rule, low-grade gliomas in adults have a greater tendency for histologic progression and more aggressive clinical behavior than those in children. With respect to genetic alterations, activating BRAF alterations and increased MAPK pathway signaling are near universal features of the circumscribed low-grade glioma group (e.g., PA and PXA). Whole exome/genome sequencing efforts and high resolution copy number platforms have also provided important biologic insights in these tumors, with adult low-grade diffuse gliomas containing frequent ATRX, TP53 mutations (astrocytomas), as well as 1p19q co-deletions, CIC, FUBP1 and TERT promoter mutations (oligodendrogliomas). Conversely, alterations in FGFR1, MYB, and MYBL1 are frequent events in pediatric low-grade diffuse gliomas. In this review we summarize our current knowledge of the diagnostic and molecular pathology of these tumors, and explore possible avenues for targeted therapeutics.
Abstract Autonomous Inflow Control Devices (AICDs) are being increasingly used for downhole produced water reduction and to increase oil recovery. AICD technology is typically fluid dependent and reacts to the change in properties of fluid flowing through it. Most AICDs react to the viscosity change of the flowing fluids and create an additional pressure drop to restrict the unwanted fluids (Kalyani et al., 2022). Downhole reduction of water produced directly reduces carbon footprint in terms of water handling, reduction of water injection and extending the well life This paper describes a methodology to estimate life of well carbon footprint and carbon intensity for oil wells installed with different inflow control well devices and will highlight benefits offered by autonomous device during installation. The data input and design modelling workflow will be described for a Density based AICD that provides active water management in multiphase production operating without electric or surface control, and reacting to the density change of the flowing mixture. The presented analysis is scalable to a Field-Level to help in assessing the overall environmental impact of Density based AICDs. A methodology and digital tool kit have been developed that allows lifecycle estimation of overall carbon footprint and carbon intensity map and trends for typical ICD completed Wells. The analysis considers all impacts of ICD installation, operation, workover and provides End-to-End estimation of overall carbon footprint. The tool kit consists of a performance calculator that selects the ideal ICD characteristics and feeds a customized reservoir interface steady state numerical simulator along with data on candidate well such as Production Logging, Permeability and Pressure-Volume-Temperature information. The output predicts zonal flow profile for optimized oil production and water choke back rates for the well, and produces time based cumulative and year-on-year carbon equivalent footprint and carbon intensity maps through predictive environmental impact calculations based on industry knowledge and published guidelines. To demonstrate the methodology, a hypothetical synthetic field model was created with assumed characteristics to allow for comparison study between different inflow control technology combinations in same conditions. The methodology is applicable to any AICD or passive ICD technology. AICDs balance inflow across the production zone during initial production and automatically restricts the rate from zones producing water later in-well life. This analysis is conducted over the full well lifecycle considering early, mid and late life stages. The resultant time-series data is converted to Well-Level carbon equivalent footprint map over time by evaluating against total oil production from the Well. Performance of passive ICD versus autonomous Density-AICD is evaluated for environmental gains in the simulated wells. This methodology can be extended to multiple wells in a cluster and provide a Field-Level carbon equivalent footprint visual heat map. Furthermore, Carbon intensity trends are derived for target Wells and Field. The results can help optimize the selection of each Density-AICD and fine tune zonal placements and choke sizes. This enables yearly carbon savings to be in line with regional and global upstream goals. This analysis assesses the environmental impact of Density-AICDs for Oil operators to review against regional and global sustainable development Goals (SDGs). This tool kit will help operations teams and executives from the Operator evaluate high impact oilfields with water breakthrough and reveal opportunities to accelerate optimization of planned and existing wells to reduce water production.
ABSTRACT Introduction Inconsistent effects of subthalamic deep brain stimulation (STN DBS) on pain, a common non-motor symptom of Parkinson’s disease (PD), may be due to variations in active contact location relative to a pain-reducing locus of stimulation. Objective To distinguish the loci of maximal effect for pain and motor improvement in the STN region. Methods We measured Movement Disorder Society Unified PD Rating Scale (MDS-UPDRS) Part I pain score (item-9), and MDS-UPDRS Part III motor score, preoperatively and 6-12 months after STN DBS. An ordinary least-squares regression model was used to examine active contact location as a predictor of follow-up pain score while controlling for baseline pain, age, dopaminergic medication, and motor improvement. An atlas-independent electric field model was applied to distinguish sites of maximally effective stimulation for pain and motor improvement. Results In 74 PD patients, mean pain score significantly improved after STN DBS ( p = 0.01). In a regression model, more dorsal active contact location was the only significant predictor of pain improvement ( R 2 = 0.17, p = 0.03). The stimulation locus for maximal pain improvement was lateral, anterior, and dorsal to that for maximal motor improvement. Conclusions More dorsal STN DBS improves pain. Stimulation of the zona incerta, a region known to modulate pain in humans, may explain this observation.
Voting is one of the most commonly used terms in contemporary age of democratic politics. The ever-increasing popularity of democratic theory and practices has even made this term a household name. In democratic systems, and their number is quite large and ever increasing, each adult citizen uses ‘voting’ as a means for expressing his approval or disapproval of governmental decisions, policies and programmers of various political parties and the qualities of the candidates who are engaged in the struggle to get the status of being the representatives of the people. The study of determinants of electoral behavior constitutes a very significant area of empirical investigation. Man is a rational creature in the philosophical sense of term; he is not so rational in the realms of his economic or political behavior. An empirical study of the determinants of electoral behavior displays the astounding fact that the behavior of man is influenced by several irrational factors and pressure groups in invoking religious and communal factors, influence of money or charismatic personality of a leader and host of other irrational forces have their definite influence on the minds of the voters. The main purpose of the present study is to focus attention on voting behavior in India and to highlight the factors that determine the voting behavior in India.
1. Voltage‐dependent inhibition of N‐type calcium currents by G‐proteins contributes importantly to presynaptic inhibition. To examine the effect of G‐proteins on key intermediary transitions leading to channel opening, we measured both gating and ionic currents arising from recombinant N‐type channels (alpha 1B, beta 1b and alpha 2) expressed in transiently transfected human embryonic kidney cells (HEK 293). Recombinant expression of a homogeneous population of channels provided a favourable system for rigorous examination of the mechanisms underlying G‐protein modulation. 2. During intracellular dialysis with GTP gamma S to activate G‐proteins, ionic currents demonstrated classic features of voltage‐dependent inhibition, i.e. strong depolarizing prepulses increased ionic currents and produced hyperpolarizing shifts in the voltage‐dependent activation of ionic current. No such effects were observed with GDP beta S present to minimize G‐protein activity. 3. Gating currents were clearly resolved after ionic current blockade with 0.1 mM free La3+, enabling this first report of gating charge translocation arising exclusively from N‐type channels. G‐proteins decreased the amplitude of gating currents and produced depolarizing shifts in the voltage‐dependent activation of gating charge movement. However, the greatest effect was to induce a approximately 20 mV separation between the voltage‐dependent activation of gating charge movement and ionic current. Strong depolarizing prepulses largely reversed these effects. These modulatory features provide telling clues about the kinetic steps affected by G‐proteins because gating currents arise from the movement of voltage sensors that trigger channel activation. 4. The mechanistic implications of concomitant G‐protein‐mediated changes in gating and ionic currents are discussed. We argue that G‐proteins act to inhibit both voltage‐sensor movement and the transduction of voltage‐sensor activation into channel opening.
