Miracle-dz/UniFAR-FTUs huggingface dataset:
A network of SMG-8, SMG-9 and SMG-1 C-terminal insertion domain regulates UPF1 substrate recruitment and phosphorylation

Mammalian nonsense-mediated mRNA decay (NMD) is a eukaryotic surveillance mechanism that degrades mRNAs containing premature translation termination codons. Phosphorylation of the essential NMD effector UPF1 by the phosphoinositide-3-kinase-like kinase (PIKK) SMG-1 is a key step in NMD and occurs when SMG-1, its two regulatory factors SMG-8 and SMG-9, and UPF1 form a complex at a terminating ribosome. Electron cryo-microscopy of the SMG-1–8–9-UPF1 complex shows the head and arm architecture characteristic of PIKKs and reveals different states of UPF1 docking. UPF1 is recruited to the SMG-1 kinase domain and C-terminal insertion domain, inducing an opening of the head domain that provides access to the active site. SMG-8 and SMG-9 interact with the SMG-1 C-insertion and promote high-affinity UPF1 binding to SMG-1–8–9, as well as decelerated SMG-1 kinase activity and enhanced stringency of phosphorylation site selection. The presence of UPF2 destabilizes the SMG-1–8–9-UPF1 complex leading to substrate release. Our results suggest an intricate molecular network of SMG-8, SMG-9 and the SMG-1 C-insertion domain that governs UPF1 substrate recruitment and phosphorylation by SMG-1 kinase, an event that is central to trigger mRNA decay.
CHEMIOSMOTIC COUPLING IN OXIDATIVE AND PHOTOSYNTHETIC PHOSPHORYLATION

The processes of oxidative and photosynthetic phosphorylation, often alternatively described as electron transport phosphorylation, consist of the flows of two sets of particles: the oxido-reduction (o/r) particles (eg. 2H, Hor 2e-), and the hydrodehydration (h/d) particles, popularly identified as < energy-rich’ bonds ( N ) terminating at adenosine triphosphate (ATP). The enzymes and catalytic carriers that channel these flows in mitochondria, chloroplasts and micro-organisms are so organized that there is a variable degree of coupling between them. The end result of the coupling between the flows through the o/r and h/d pathways in oxidative phosphorylation in mitochondria is that, for the equivalent of each pair of electrons traversing the respiratory chain, up to 3 anhydro-bond equivalents may normally traverse the h/d pathway from adenosine diphosphate plus inorganic phosphate (ADP +Pi) to water. This is usually stated in the form that the P/O or P/2e quotient has a limiting value of 3. In photosynthetic phosphorylation the stoichiometry is less certain, and it is thought that either one or two anhydro-bond equivalents may traverse the h/d pathway per electron pair equivalent traversing the o/r pathway (see Vernon & Avron, 1965; Winget, Izawa & Good, 1965; Baltscheffsky, 1966). It has long been believed that coupling between oxido-reduction and phosphorylation depends upon the existence of certain ‘ energy-rich ’ chemical intermediatesC, I,, C, N I,, C, I,, involving the respiratory carriers C,, C,, C, and unknown components I,, I,, I, (conventions of Lee & Ernster, 1964)-that are common to the o/r and h/d pathways (Slater, 1953, 1958; Chance & Williams, 1956; Lehninger et al. 1958; Racker, 1961; Green & Fleischer, 1962). The attention of research workers has therefore been concentrated upon the idea that, if only the identity of these inter-
Burnout Is Associated with Reduced Parasympathetic Activity and Reduced HPA Axis Responsiveness, Predominantly in Males

There is mounting evidence that burnout is a risk factor for cardiovascular disease (CVD). Stress-related dysregulation of the sympathetic and parasympathetic system and the hypothalamic pituitary adrenal (HPA) axis may explain the enhanced risk for CVD. To test this hypothesis, 55 patients (34 males and 21 females) with burnout on sickness absence and 40 healthy participants (16 males and 24 females) were exposed to a psychosocial stressor consisting of mental arithmetic and public speech. Physiological variables (i.e., blood pressure, heart rate, cardiac output, vascular resistance, cortisol, and alpha-amylase) were measured. Basal levels, reactivity, and recovery were compared between groups. In male patients, baseline systolic blood pressure was higher, whereas basal alpha-amylase and cortisol reactivity were lower than in healthy males. In female patients, a tendency for lower basal cortisol was found as compared to healthy females. Furthermore, reduced basal heart rate variability and a trend for elevated basal cardiac output were observed in both male and female patients. Burnout is characterised by dysregulation of the sympathetic and parasympathetic system and the HPA axis, which was more pronounced in males than in females. This study further supports burnout as being a risk factor for CVD through dysregulation of the sympathetic and parasympathetic system and the HPA axis.
A Survey of Insulin-Dependent Diabetes—Part I: Therapies and Devices

This paper surveys diabetes therapies from telemedicine viewpoint. In type 1 diabetes therapies, the exogenous insulin replacement is generally considered as a primary treatment. However, the complete replacement of exogenous insulin is still a challenging issue because of its complexity of modeling the dynamics, which is typically modeled nonlinearly. On the other hand, thanks to the progress of medical devices, currently the diabetes therapies are being automated. These medical devices include automated insulin pumps and blood glucose sensors. Insulin pumps are designed to create artificial insulin perfusion while they largely rely on the blood glucose profile measurements and these measurements are achieved by one or more blood glucose sensors. The blood glucose measurements are also important for the insulin-dependent diabetes therapies. An insulin pump along with sensors establishes a good feedback system providing the appropriate amount of the exogenous insulin on demand. Controlling the amount of exogenous insulin to suppress the blood glucose levels requires complicated computations. This paper mostly explains both type 1 and 2 diabetes and their mechanisms accompanied by descriptions of diabetes therapy and medical devices currently utilized in the therapy.
Magnetic resonance imaging abnormalities associated with vigabatrin in patients with epilepsy

Purpose: Vigabatrin used to treat infantile spasms (IS) has been associated with transient magnetic resonance imaging (MRI) abnormalities. We carried out a retrospective review to better characterize the frequency of those abnormalities in IS and in children and adults treated with vigabatrin for refractory complex partial seizures (CPS).
Microsoft Cambridge at TREC-9: Filtering Track

Apart from a short description of our Query Track contribution, this report is concerned with the Adaptive Filtering track only. There is a separate report in this volume [1] on the Microsoft Research Cambridge participation in QA track. A number of runs were submitted for the Adaptive Filtering track, on all tasks (adaptive filtering, batch filtering and routing; three separate query sets; two evaluation measures). The filtering system is somewhat more advanced than the one used for TREC–8, and includes query modification and a more highly developed scheme for threshold adaptation. A number of diagnostic runs are also reported here.
Power and Predictive Accuracy of Polygenic Risk Scores

Polygenic scores have recently been used to summarise genetic effects among an ensemble of markers that do not individually achieve significance in a large-scale association study. Markers are selected using an initial training sample and used to construct a score in an independent replication sample by forming the weighted sum of associated alleles within each subject. Association between a trait and this composite score implies that a genetic signal is present among the selected markers, and the score can then be used for prediction of individual trait values. This approach has been used to obtain evidence of a genetic effect when no single markers are significant, to establish a common genetic basis for related disorders, and to construct risk prediction models. In some cases, however, the desired association or prediction has not been achieved. Here, the power and predictive accuracy of a polygenic score are derived from a quantitative genetics model as a function of the sizes of the two samples, explained genetic variance, selection thresholds for including a marker in the score, and methods for weighting effect sizes in the score. Expressions are derived for quantitative and discrete traits, the latter allowing for case/control sampling. A novel approach to estimating the variance explained by a marker panel is also proposed. It is shown that published studies with significant association of polygenic scores have been well powered, whereas those with negative results can be explained by low sample size. It is also shown that useful levels of prediction may only be approached when predictors are estimated from very large samples, up to an order of magnitude greater than currently available. Therefore, polygenic scores currently have more utility for association testing than predicting complex traits, but prediction will become more feasible as sample sizes continue to grow.
A Comparison of the Special Wetting Property between Locust and Butterfly Wing

The microstructure, wettability and chemical composition of butterfly and locust wing surfaces were investigated by a scanning electron microscope (SEM), a contact angle meter and a Fourier transform infrared spectrometer (FT-IR). The hydrophobicity models were established on the basis of Cassie equation. The wetting mechanism was comparatively discussed from the perspective of biological coupling. The butterfly and the locust wing surfaces are composed of naturally hydrophobic materials, but exhibit different complex wettability. The butterfly wing surface is of low adhesion (sliding angle 1~4°) and superhydrophobicity (contact angle 150.5~156.2°), while the locust wing surface is of extremely high adhesion (sliding angle>180°) and superhydrophobicity (contact angle 150.6~154.8°). The complex wettability of the wing surfaces ascribes to coupling effect of hydrophobic material and rough structure. The butterfly and locust wings can be used as bio-templates for design and preparation of biomedical functional surface, intelligent interfacial material and no-loss microfluidic transport channels. Introduction In the last few years, the interfacial materials with desirable properties and functions have attracted tremendous interest due to valuable theoretical importance and a wide variety of applications in industrial, military, biomedical and domestic fields [1~3]. After long-term natural evolution and selection, many animals and plants have possessed special surface micro/nanostructures, which endow the creatures with multi-functions. Inspired by the wettability of various bio-surfaces such as lotus leaf, lots of superhydrophobic and self-cleaning materials have been artificially prepared [4~ 7]. The superhydrophobic material with high adhesion can be used as “mechanical hand” in the field of no-loss microfluidic transport. As one of the most complicated three-dimensional periodical substrates in nature, the insect wing has become a popular biomimetic fabrication template because of the superior characteristics [8]. In this work we investigated the chemical composition, microstructure, hydrophobicity and adhesion of butterfly and locust wing surfaces, found different complex wettability. The wetting mechanism was discussed comparatively from the perspective of biological coupling. The results may bring inspiration for bionic design and fabrication of smart biomedical materials. 447 This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/). Copyright © 2017, the Authors. Published by Atlantis Press. 2nd International Conference on Biomedical and Biological Engineering 2017 (BBE 2017) Advances in Biological Sciences Research (ABSR), volume 4
Stability of dynamic brain models in neuropercolation approximation

In this paper, the basic building blocks of the intentional neurodynamics cycle are studied using probabilistic cellular automata. We apply the mean field neuropercolation model to describe the dynamics of coupled excitatory-inhibitory neural populations. The model exhibits a phase transition between a background point attractor and narrow-band (limit-cycle) behavior, depending of the choice of system parameters. Metastable dynamics near criticality is investigated. We show the existence of various regions with unstable and multiple stable equilibria. The results are relevant to modeling cognitive phase transitions observed in brains during awareness experience.
Comparison of kinematic and kinetic parameters calculated using a cluster-based model and Vicon’s plug-in gait

Gait analysis is an important clinical tool. A variety of models are used for gait analysis, each yielding different results. Errors in model outputs can occur due to inaccurate marker placement and skin motion artefacts, which may be reduced using a cluster-based model. We aimed to compare a custom-made cluster model (ClusBB) with Vicon’s plug-in gait. A total of 21 healthy subjects wore marker sets for the ClusBB and plug-in gait models simultaneously while walking on a 6-m walkway. Marker and force plate data were captured synchronously and joint angles/moments were calculated using both models. There was good correlation between the models (coefficient of multiple correlations > 0.65) and good intra-session correlation for both models (coefficient of multiple correlations > 0.80). Inter-subject variability was high, ranging from 15° to 40° in the sagittal plane and 11° to 52° in the coronal and transverse planes. Intra-subject variability was small for both ClusBB and plug-in gait models. Inter-subject variance tended to be high in both models for knee abduction/adduction, but particularly so for plug-in gait, suggesting that a cluster-based model may reduce the variability. The inter-subject variance in out-of-sagittal plane data is of particular importance clinically, given the reliance on these datasets in clinical decision-making.
Perspectives for Reactive Molding of PPA as Matrix for High-performance Composite Materials

While liquid composite molding (LCM) technologies for thermoset composites are increasingly used for manufacturing high quality structural components, LCM technologies based on thermoplastic matrices are still in development. Reactive thermoplastic LCM processes are at present applicable only to a few engineering polymers. This work presents perspectives for reactive molding of a high-temperature resistant polyphthalamide (PPA). Thermoanalytical, rheological, and optical tests were performed to assess the behavior of low-melting PA 6T/6I oligomers with increasing temperature and to monitor the polymerization and crystallization reactions. The raw oligomeric material first undergoes a solid-liquid phase transition at around 135 C. At this stage, it shows a shear-thinning behavior and its viscosity is around 102 Pa s. At higher temperatures, the viscosity of the oligomeric melt decreases further until a high temperature crystallization process occurs at about 180 C. Polymerization starts at about 220 C and ends at 290 C. During the reaction the polymer crystallizes as soon as it is formed with an achievable degree of crystallinity considerably higher than that of melt-crystallized samples. In accordance with the results, a viable processing technology based on powder impregnated intermediate materials is proposed.
Cytomegalovirus-Infected Cells Resist T Cell Mediated Killing in an HLA-Recognition Independent Manner

In order to explore the potential of HLA-independent T cell therapy for human cytomegalovirus (HCMV) infections, we developed a chimeric antigen receptor (CAR) directed against the HCMV encoded glycoprotein B (gB), which is expressed at high levels on the surface of infected cells. T cells engineered with this anti-gB CAR recognized HCMV-infected cells and released cytokines and cytotoxic granules. Unexpectedly, and in contrast to analogous approaches for HIV, Hepatitis B or Hepatitis C virus, we found that HCMV-infected cells were resistant to killing by the CAR-modified T cells. In order to elucidate whether this phenomenon was restricted to the use of CARs, we extended our experiments to T cell receptor (TCR)-mediated recognition of infected cells. To this end we infected fibroblasts with HCMV-strains deficient in viral inhibitors of antigenic peptide presentation and targeted these HLA-class I expressing peptide-loaded infected cells with peptide-specific cytotoxic T cells (CTLs). Despite strong degranulation and cytokine production by the T cells, we again found significant inhibition of lysis of HCMV-infected cells. Impairment of cell lysis became detectable 1 day after HCMV infection and gradually increased during the following 3 days. We thus postulate that viral anti-apoptotic factors, known to inhibit suicide of infected host cells, have evolved additional functions to directly abrogate T cell cytotoxicity. In line with this hypothesis, CAR-T cell cytotoxicity was strongly inhibited in non-infected fibroblasts by expression of the HCMV-protein UL37x1, and even more so by additional expression of UL36. Our data extend the current knowledge on Betaherpesviral evasion from T cell immunity and show for the first time that, beyond impaired antigen presentation, infected cells are efficiently protected by direct blockade of cytotoxic effector functions through viral proteins.
Bone Tissue Properties Measurement by Reference Point Indentation in Glucocorticoid‐Induced Osteoporosis

Glucocorticoids, widely used in inflammatory disorders, rapidly increase bone fragility and, therefore, fracture risk. However, common bone densitometry measurements are not sensitive enough to detect these changes. Moreover, densitometry only partially recognizes treatment‐induced fracture reductions in osteoporosis. Here, we tested whether the reference point indentation technique could detect bone tissue property changes early after glucocorticoid treatment initiation. After initial laboratory and bone density measurements, patients were allocated into groups receiving calcium + vitamin D (Ca+D) supplements or anti‐osteoporotic drugs (risedronate, denosumab, teriparatide). Reference point indentation was performed on the cortical bone layer of the tibia by a handheld device measuring bone material strength index (BMSi). Bone mineral density was measured by dual‐energy X‐ray absorptiometry (DXA). Although Ca+D‐treated patients exhibited substantial and significant deterioration, risedronate‐treated patients exhibited no significant change, and both denosumab‐ and teriparatide‐treated participants exhibited significantly improved BMSi 7 weeks after initial treatment compared with baseline; these trends remained stable for 20 weeks. In contrast, no densitometry changes were observed during this study period. In conclusion, our study is the first to our knowledge to demonstrate that reference point indentation is sensitive enough to reflect changes in cortical bone indentation after treatment with osteoporosis therapies in patients newly exposed to glucocorticoids. © 2015 American Society for Bone and Mineral Research.
Trellis Coded Spatial Modulation

Trellis coded modulation (TCM) is a well known scheme that reduces power requirements without any bandwidth expansion. In TCM, only certain sequences of successive constellation points are allowed (mapping by set partitioning). The novel idea in this paper is to apply the TCM concept to the antenna constellation points of spatial modulation (SM). The aim is to enhance SM performance in correlated channel conditions. SM considers the multiple transmit antennas as additional constellation points and maps a first part of a block of information bits to the transmit antenna indices. Therefore, spatial multiplexing gains are retained and spectral efficiency is boosted. The second part of the block of information bits is mapped to a complex symbol using conventional digital modulation schemes. At any particular time instant, only one antenna is active. The receiver estimates the transmitted symbol and the active antenna index and uses the two estimates to retrieve the original block of data bits. In this paper, TCM partitions the entire set of transmit antennas into sub-sets such that the spacing between antennas within a particular sub-set is maximized. The scheme is called trellis coded spatial modulation (TCSM). Tight analytical performance bounds over correlated fading channels are proposed in this paper. In addition, the performance and complexity of TCSM is compared to the performance of SM, coded V-BLAST (vertical Bell Labs layered space-time) applying near optimum sphere decoder algorithm, and Alamouti scheme combined with TCM. Also, the performance of all schemes with turbo coded modulation is presented. It is shown that under the same spectral efficiency, TCSM exhibits significant performance enhancements in the presence of realistic channel conditions such as Rician fading and spatial correlation (SC). In addition, the complexity of the proposed scheme is shown to be 80% less than the V-BLAST complexity.
Imaging through scattering media with single-pixel detection

We describe a method to image objects through scattering media based on single-pixel detection and microstructured illumination. Spatial light modulators are used to project a set of microstructured light patterns onto the sample. The image is retrieved computationally from the photocurrent fluctuations provided by a single-pixel detector. This technique does not require coherent light, raster scanning, time-gated detection or a-priori calibration process. We review several optical setups developed by our research group in the last years with particular emphasis in a new optical system based on a double-pass configuration and in the combination of single-pixel imaging with Fourier filtering.
Elevated CETP Activity Improves Plasma Cholesterol Efflux Capacity From Human Macrophages in Women

Objective—We aim to identify the impact of endogenous cholesteryl ester transfer protein (CETP) activity on plasma capacity to mediate free cholesterol efflux from human macrophages. Methods and Results—Endogenous plasma CETP activity was measured in a population of 348 women. We defined a low CETP group corresponding to subjects displaying an endogenous plasma CETP activity within the first tertile and a high CETP group corresponding to subjects with an endogenous plasma CETP activity within the third tertile. Subjects from the high CETP activity group displayed a significant increase in the capacity of their plasma (+8.2%; P=0.001) to mediate cholesterol efflux from human acute monocytic leukemia cell line human macrophages and from ATP-binding cassette transporter A1-dependent pathway (+23.4%; P=0.0001) as compared with those from the low CETP activity group. Multivariate analyses revealed that the impact of CETP activity was independent of plasma lipids levels. Pre–&bgr;1-high-density lipoprotein concentrations were significantly elevated (+29.6%; P=0.01) in the high CETP activity group as compared with the low CETP activity group. A positive correlation between pre–&bgr;1-high-density lipoprotein levels and plasma efflux efficiency from human acute monocytic leukemia cell line human macrophages was observed (r=0.29, P=0.02). Conclusion—CETP leading to the improvement of plasma efflux capacity, as a result of efficient pre–&bgr;-high-density lipoprotein formation and ATP-binding cassette transporter A1 efflux, should be preserved to prevent lipid accumulation in human macrophages.