Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanism of pharmacochaperoning in a mammalian KATP channel revealed by cryo-EM

ATP-sensitive potassium (KATP) channels composed of a pore-forming Kir6.2 potassium channel and a regulatory ABC transporter sulfonylurea receptor 1 (SUR1) regulate insulin secretion in pancreatic β-cells to maintain glucose homeostasis. Mutations that impair channel folding or assembly prevent cell surface expression and cause congenital hyperinsulinism. Structurally diverse KATP inhibitors are known to act as pharmacochaperones to correct mutant channel expression, but the mechanism is unknown. Here, we compare cryoEM structures of a mammalian KATP channel bound to pharmacochaperones glibenclamide, repaglinide, and carbamazepine. We found all three drugs bind within a common pocket in SUR1. Further, we found the N-terminus of Kir6.2 inserted within the central cavity of the SUR1 ABC core, adjacent the drug binding pocket. The findings reveal a common mechanism by which diverse compounds stabilize the Kir6.2 N-terminus within SUR1’s ABC core, allowing it to act as a firm ‘handle’ for the assembly of metastable mutant SUR1-Kir6.2 complexes.
Cannabis for Chronic Pain: We Simply Don't Know.

To understand these different interpretations, the devil really is in the details. First, it is important to distinguish neuropathic from nociceptive pain. The latter has largely been unstudied, but the two have been conflated in a summary of findings from two widely publicized reports [1,2]. Second, the dosages and formulations of cannabis have varied across studies and do not closely approximate what is typically available to and used by consumers. Finally, the trial duration is important to consider because chronic pain is likely to require prolonged treatment. Among the studies that reported therapeutic benefit in neuropathic pain, most had very short follow-up, on the order of hours to days [2].
Determining the Corticospinal Responses to Single Bouts of Skill and Strength Training.

Mason, J, Frazer, AK, Jaberzadeh, S, Ahtiainen, JP, Avela, J, Rantalainen, T, Leung, M, and Kidgell, DJ. Determining the corticospinal responses to single bouts of skill and strength training. J Strength Cond Res XX(X): 000-000, 2019-Neuroplastic changes in the primary motor cortex accompany performance improvements following motor practice. Recent evidence suggests that the corticospinal responses to strength and skill training are similar, following both a single session and repeated bouts of training, promoting discussion that strength training is a form of motor learning. However, these findings are limited by the lack of a light-load strength training group. Therefore, the aim of the current study was to determine whether a single session of heavy-load strength training, light-load strength training or skill training differentially modulates the corticospinal pathway. Transcranial magnetic stimulation was used to assess the excitatory and inhibitory circuitry of the motor cortex following a single session of skill training, and following a single session of light-load and heavy-load strength training. Following a single session of training, participants in all groups experienced comparable increases in corticospinal excitability (ranging from 38 to 46%, all p < 0.05); however, disparity was observed in the inhibitory responses. Corticospinal inhibition was reduced in all 3 single-sessions, although to a greater magnitude in the heavy-load and skill-training sessions (22 and 18% respectively, compared with 11% following light-load training, all p < 0.05). Short-interval intracortical inhibition was reduced immediately following single sessions of heavy-load strength training (40% p < 0.05) and skill training (47% p < 0.05), but remained unchanged the following light-load strength training session. It appears that the corticospinal responses to single sessions of different types of strength and skill training are task-dependent. These findings reinforce the notion that strength training, at least when heavily-loaded, can be considered a form of motor learning, potentially because of the sensory feedback involved.
Toward Better Health Outcomes in Rural and Under-served Areas: L. V. Prasad Eye Institute’s Diagonal Model of Glaucoma Care

ABSTRACT Purpose: L. V. Prasad Eye Institute has adopted horizontal approach of eye care delivery for the past 22 years at one of its rural secondary centers. The recent implementation of a diagonal model for enhancing glaucoma care at this center and its outcomes are reported. Methods: This was a retrospective case-control study. We included newly and consecutively diagnosed adult glaucoma patients. A comprehensive ophthalmologist provided glaucoma care. During the study period, an experienced glaucoma specialist supported the care for 2 days every month in a structured format that consisted of triaging glaucoma patients for defined protocols of therapy along with hands-on and remote online guidance to the comprehensive ophthalmologist. The data from the worst or single eye were analyzed. Results: We have included 231 patients (151 study and 80 historical controls). Sixty (75%) control patients were managed at the study center and 20 (25%) were referred. The comprehensive ophthalmologist managed 70 (48.2%) study patients and co-managed 75 (51.7%) with the glaucoma specialist. The latter changed the diagnosis in 15 eyes and altered the treatment plan in 44 eyes. Six were excluded. Successful outcome was achieved in 52 (65%) eyes in the control group and 120 (84.5%) eyes in the study group (P < .01). Additionally, study group did better in terms of case detection rate, compliance to treatment and saving on expenses for patients. Conclusion: The new model has shown better clinical outcomes of glaucoma care in an under-served geographic area. The model has the potential for wider applicability.
Strategies to Augment Natural Killer (NK) Cell Activity against Solid Tumors

The immune system plays a crucial role to prevent local growth and dissemination of cancer. Therapies based on activating the immune system can result in beneficial responses in patients with metastatic disease. Treatment with antibodies targeting the immunological checkpoint axis PD-1 / PD-L1 can result in the induction of anti-tumor T cell activation leading to meaningful long-lasting clinical responses. Still, many patients acquire resistance or develop dose-limiting toxicities to these therapies. Analysis of tumors from patients who progress on anti-PD-1 treatment reveal defective interferon-signaling and antigen presentation, resulting in immune escape from T cell-mediated attack. Natural killer (NK) cells are innate lymphocytes that can kill tumor cells without prior sensitization to antigens and can be activated to kill tumor cells that have an impaired antigen processing and presentation machinery. Thus, NK cells may serve as useful effectors against tumor cells that have become resistant to classical immune checkpoint therapy. Various approaches to activate NK cells are being increasingly explored in clinical trials against cancer. While clinical benefit has been demonstrated in patients with acute myeloid leukemia receiving haploidentical NK cells, responses in patients with solid tumors are so far less encouraging. Several hurdles need to be overcome to provide meaningful clinical responses in patients with solid tumors. Here we review the recent developments to augment NK cell responses against solid tumors with regards to cytokine therapy, adoptive infusion of NK cells, NK cell engagers, and NK cell immune checkpoints.
Survey of Human Motion Analysis

With the rapid development of computer vision,analysis of the human movement has been widely noted in computer vision areas.This research on the human movement is about the whole human motion,including extracting joint points first,then trcking the feature points and calculating the 3D coordinates of the points and display.The paper introduces from current situation of the three aspects.
Action Recognition and Activity Understanding:A Review

As the "Human-centered computing" is getting more popular and novel applications are evolving,action recognition and activity understanding are attracting researchers in the field of computer vision.In this paper,we review the state-of-the-art work on action and activity analysis with focus on three parts: Definition of activity,low-level motion features extraction and action representation,and reasoning method for activity understanding.Furthermore,open problems for future research and potential directions are discussed.
Research for Reputation Models in VANET

As a typical open distributed system,the Vehicular Ad hoc NETworks(VANET) are composed ephemerally due to their high mobility.Vehicle nodes in the VANET are facing with various malicious nodes and hard to choose trustworthy collaborative nodes in applications.To solve these problems,we design VANET application specified reputation models(VASRep) to qualifiedly evaluate the reputation of the nodes.Through merging various types of information sources in VANET,VASRep can express the node′s trustworthiness more accurately.According to the authority units′ recommendation,VASRep is more suitable to VANET environments.Finally,the analysis and evaluation show that our model outperforms the existing solutions in terms of performance and resisting the attack of malicious nodes.
Semantic Web Architecture Using Side Information

In many text mining applications, the side-information is available along with the text documents, namely document provenance information, user-access behavior from web logs, the links in the document and other attributes.This attributes may contain large amount of information in the clustering purposes. It is very difficult to estimate the relative information, when some of information is noisy data. It can be risky to incorporate side-information into the mining process, as it can either improve the quality of the representation for the mining process, or can add noise to the process. An algorithm which combines classical partitioning algorithms with probabilistic models is used in order to create an effective clustering approach. The proposed idea is to build an information system on the web to extract knowledge from the available information through the designed portal. The result helps the user to obtain the greatest amount of possible integrated and interrelated information.
An experimental analysis of a set of compiler algorithms

The thesis of this dissertation is that experimental analysis in computer science is an essential component of understanding algorithmic behavior. In three different experiments, we compare and contrast well-chosen algorithms and show empirical evidence of performance differences. In all cases herein, the algorithms that were assumed to be the best are shown to have superior, sometimes surprising alternatives, justifying our thesis. In each case, we developed a set of solutions and evaluated and refined them until we discovered better methods. In the first experiment, we examine different methods for building an interference graph, the pivotal structure of a graph-coloring register allocator. Our results show that a twenty-year-old assumption about the graph's characteristics is flawed, and we show extensive data to explain the best way to build this graph. In the second experiment, we take an O(n 2) algorithm for computing dominance and show how to make it run, in general, faster than the commonly used dominator algorithm due to Lengauer and Tarjan, which runs in time proportional to the inverse of Ackermann's function. The dominance work led to our third experiment, which seeks to show the best way to compute iterative data-flow analyses. There is a well understood theoretical specification due to Kam and Ullman that bounds the time necessary to compute specific types of data-flow equations. We compare their algorithm against a simple worklist algorithm that takes its intuition from a study of how Kam and Ullman's algorithm propagates information, and we show that the worklist algorithm is faster, in practice. In many ways, the value of this work is in the engineering improvements to necessary and complicated phases of the compiler. *This work is based in part upon work supported by the Texas Advanced Technology Program under Grant No. 003604-015 and by Darpa through Army Contract DABT63-95-C-0115.
Digital Processing of Analog Information Adopting Time-Mode Signal Processing

ii To Extend the digital implementation of TMSP to a wider range of applications, the comprehensive design of a unity gain dual-path time-to-time integrator (accumulator) is demonstrated. This integrator is then used to implement a digital second-order delta-sigma modulator. Finally, to demonstrate the advantage of TMSP, a very low power and compact tunable interface for capacitive sensors is presented that is composed of a number of delay blocks associated with typical logic gates. All the proposed theories are supported by experimental results and post-layout simulations. The emphasis on the digital construction of the proposed circuits has been the first priority of this thesis. Having the building blocks implemented with a digital structure, provides the feasibility of a simple, synthesizable, and reconfigurable design where affordable circuit calibrations can be adopted to remove the effects of process variations.
Mechanical Proofreading: A General Mechanism to Enhance the Fidelity of Information Transfer Between Cells

The cells and receptors of the immune system are mechanically active. Single molecule force spectroscopy, traction force microscopy, and molecular tension probe measurements all point to the importance of piconewton (pN) molecular forces in immune function. For example, forces enhance the ability of a T cell to discriminate between nearly identical antigens. The role of molecular forces at these critical immune recognition junctions is puzzling because mechanical forces generally facilitate bond dissociation, potentially increasing the difficulty for a receptor to recognize its cognate antigen. The advantage molecular forces confer in the process of immune recognition is not clear. Why would cells expend energy to exert force on the critical, but tenuous bonds that mediate immune surveillance? Do molecular forces provide some advantage to the immune system? The premise of this review is that molecular forces provide a specificity advantage to immune cells. Inspired by the recent discovery that receptor forces regulate immune signaling in T cells and B cells, we dub this notion "mechanical proofreading," akin to more classic kinetic proofreading models. During the process of mechanical proofreading, cells exert pN receptor forces on receptor-ligand interactions, deliberately increasing the energy cost of the immune recognition process in exchange for increased specificity of signaling. Here, we review the role of molecular forces in the immune system and suggest how these forces may facilitate mechanical proofreading to increase the specificity of the immune response.
Life Cycle Costing of Alternative Value Chains of Biomass Energy for Cooking in Kenya and Tanzania

In near future, wood-based biomass energy will remain the main cooking energy for households in East Africa, especially for poor households due to its availability and affordability. Alternative biomass fuels however exist. Economic viability of these alternatives is important due to its potential to influence their adoption and sustained use. This research evaluates the economic efficiency of firewood, charcoal, biogas, jatropha oil, and crop residue briquettes value chains in the rural-urban contexts of Kitui, Kenya, and Moshi, Tanzania, using Life Cycle Costing (LCC) methodology. LCC helps to identify areas along the value chains where costs occur and where improvements are feasible. Jatropha oil manual value chain has the highest cost. Firewood use with improved cook stoves is cost efficient. In Moshi’s rural context, royalty fees increases cost of charcoal. Similarly, biogas in Kitui is less likely to be economically viable. Briquettes however have a competitive advantage over charcoal. The costs are dominated by fuel provision compared to cost of stoves. Therefore, payment schemes that improve adoption of improved stoves perceived as expensive will substantially reduce fuel cost. Enhancing availability and accessibility of technologies such as briquette presses will enhance biomass energy access and provide a source of income for households.
A Unique Hastening Communication-Bound Sparse Repeatable Solver

This paper presents an organized procedure to pick this algorithmic parameter k, which supplies communication-computation compromise on hardware accelerators like FPGA and GPU. While k iterations from the iterative solver could be unrolled to provided decrease in communication cost, the extent of the unrolling is dependent around the underlying architecture, its memory model, and also the development in redundant computation. Buying and selling communication with redundant computation can boost the plastic efficiency of FPGAs and GPUs in speeding up communication-bound sparse iterative solvers. With an NVidia C2050 GPU, we demonstrate a speedup over standard iterative solvers for a variety of benchmarks which this speedup is restricted through the development in redundant computation. In comparison, for FPGAs, we produce an architecture-aware formula that limits off-nick communication but enables communication between your processing cores. This reduces redundant computation and enables large k and therefore greater speedups. Our method for FPGA supplies a speedup over same-generation GPU products where k is selected carefully for architectures for a variety of benchmarks. We offer predictive models to know this compromise and show how careful choice of k can result in performance improvement that otherwise demands significant rise in memory bandwidth.
Elemental and Configural Processes in Patterning Discrimination Learning

Three experiments used appetitive conditioning with rats to examine the involvement of elemental and configural processes in positive and negative patterning discriminations. The first experiment demonstrated that negative and, to some extent, positive patterning discriminations were learned more rapidly when these discriminations consisted of stimulus elements that had previously been the reinforced as opposed to the non-reinforced elements of a simple discrimination. Experiment 2 revealed an excitatory summation effect during the early phase of negative patterning learning that depended upon discrimination pretraining. The final experiment demonstrated faster discrimination learning between the compound and the less salient, rather than the more salient, element of an instrumental patterning task. The present set of results were interpreted as reflecting the possibility, consistent with connectionist theory, that internal representations of the conditioned stimuli change over the course of a patterning discrimination.
Comparative analysis of KPC-2-encoding chimera plasmids with multi-replicon IncR:IncpA1763-KPC:IncN1 or IncFIIpHN7A8:IncpA1763-KPC:IncN1

Background IncR, IncFII, IncpA1763-KPC, and IncN1 plasmids have been increasingly found among Enterobacteriaceae species, but plasmids with hybrid structures derived from the above-mentioned incompatibility groups have not yet been described. Methods Plasmids p721005-KPC, p504051-KPC, and pA3295-KPC were fully sequenced and compared with previously sequenced related plasmids pHN84KPC (IncR), pKPHS2 (IncFIIK), pKOX_NDM1 (IncFIIY), pHN7A8 (IncFIIpHN7A8), and R46 (IncN1). Results The backbone of p721005-KPC/p504051-KPC was a hybrid of the entire 10-kb IncR-type backbone from pHN84KPC, the entire 64.3-kb IncFIIK-type maintenance, and conjugal transfer regions from pKPHS2, a 15.5-kb IncFIIY-type maintenance region from pKOX_NDM1 and a 5.6-kb IncpA1763-KPC-type backbone region from pA1763-KPC, and it contained a primary IncR replicon and two auxiliary IncpA1763-KPC and IncN1 replicons. The backbone of pA3295-KPC was a hybrid of a 7.2-kb IncFIIpHN7A8-type backbone region from pHN7A8, the almost entire 33.3-kb IncN1-type maintenance and conjugal transfer regions highly similar to R46, a 26.2-kb IncFIIK-type maintenance regions from pKPHS2, the above 15.5-kb IncFIIY-type maintenance region, and the above 5.6-kb IncpA1763-KPC-type backbone region, and it contained a primary Inc-FIIpHN7A8 replicon and two auxiliary IncpA1763-KPC and IncN1 replicons. Each of p721005-KPC, p504051-KPC, and pA3295-KPC acquired a wealth of accessory modules, carrying a range of intact and residue mobile elements (such as insertion sequences, unit transposons, and integrons) and resistance markers (such as blaKPC, tetA, dfrA, and qnr). Conclusion In each of p721005-KPC, p504051-KPC, and pA3295-KPC, multiple replicons in coordination with maintenance and conjugation regions of various origins would maintain a broad host range and a stable replication at a steady-state plasmid copy number.
THROUGHPUT AND LATENCY PERFORMANCE OF IEEE 802.11E WITH 802.11A, 802.11B, AND 802.11G PHYSICAL LAYERS

IEEE 802.11e is an amendment of the medium-access control (MAC) layer of the standard for wireless local area networking IEEE 802.11. The goal of 802.11e is to provide 802.11 networks with Quality of Service (QoS). 802.11 has three physical layers (PHY) of practical importance: 802.11b, 802.11a, and 802.11g. 802.11a and 802.11g provide data rates between 6 and 54 Mbps, and 802.11b provides data rates of 5.5 Mbps and 11 Mbps. However these data rates are not the actual throughput. The actual throughput that a user will experience will be lower. The throughput depends on both the PHY and MAC layers. It is important to estimate what exactly is the throughput when the physical layer is 802.11a, 802.11b, or 802.11g, and the MAC layer is 802.11e. In other words, how does providing QoS change the throughput for each of the three physical layers? In this paper we provide answers to this problem. Analytic formulae are derived. The maximum achievable throughput and minimum delay involved in data transfers are determined. The obtained results have further significance for the design of high-throughput wireless protocols.
Multiple-platform localization and map building

This paper presents current work on decentralized data fusion (DDF) applied to multiple unmanned aerial vehicles. The benefits of decentralizing algorithms, particularly in this field, are enormous. At a mission level, multiple aircraft may fly together sharing information with one another in order to produce more accurate and coherent estimates, and hence increase the chances of success. At the single platform level, algorithms may be decentralized throughout the airframe reducing the probability of catastrophic failure by eliminating the dependency on a particular central processing facility. To this end, a complex simulator has been developed to test and evaluate decentralized picture compilation, platform localization and simultaneous localization and map building (SLAM) algorithms which are to be implemented on multiple airborne vehicles. This simulator is both comprehensive and modular, enabling multiple platforms carrying multiple distributed sensors to be modeled and interchanged easily. The map building and navigation algorithms interface with both the simulator and the real airframe in exactly the same way in order to evaluate the actual flight code as comprehensively as possible. Logged flight data can also be played back through the simulator to the navigation routines instead of simulated sensors. This paper presents the structure of both the simulator and the algorithms that have been developed. An example of decentralized map building is included, and future work in decentralized navigation and SLAM systems is discussed.