Miracle-dz/UniFAR-FTUs huggingface dataset:
Frequency and function in the basal ganglia: the origins of beta and gamma band activity

Neuronal oscillations in the basal ganglia have been observed to correlate with behaviours, although the causal mechanisms and functional significance of these oscillations remain unknown. We present a novel computational model of the healthy basal ganglia, constrained by single unit recordings from non‐human primates. When the model is run using inputs that might be expected during performance of a motor task, the network shows emergent phenomena: it functions as a selection mechanism and shows spectral properties that match those seen in vivo. Beta frequency oscillations are shown to require pallido‐striatal feedback, and occur with behaviourally relevant cortical input. Gamma oscillations arise in the subthalamic–globus pallidus feedback loop, and occur during movement. The model provides a coherent framework for the study of spectral, temporal and functional analyses of the basal ganglia and lays the foundation for an integrated approach to study basal ganglia pathologies such as Parkinson's disease in silico.
Bacterial GRAS domain proteins throw new light on gibberellic acid response mechanisms

SUMMARY Gibberellic acids (GAs) are key plant hormones, regulating various aspects of growth and development, which have been at the center of the 'green revolution'. GRAS family proteins, the primary players in GA signaling pathways, remain poorly understood. Using sequence-profile searches, structural comparisons and phylogenetic analysis, we establish that the GRAS family first emerged in bacteria and belongs to the Rossmann fold methyltransferase superfamily. All bacterial and a subset of plant GRAS proteins are likely to function as small-molecule methylases. The remaining plant versions have lost one or more AdoMet (SAM)-binding residues while preserving their substrate-binding residues. We predict that GRAS proteins might either modify or bind small molecules such as GAs or their derivatives. CONTACT aravind@ncbi.nlm. nih.gov SUPPLEMENTARY INFORMATION Supplementary Material for this article is available at Bioinformatics online.
A single-supply sub-threshold level shifter with an internal supply feedback loop for multi-voltage applications

A single-supply level shifter with an internal supply feedback loop, which can shift an input signal from the sub-threshold level to the above-threshold level, is presented in this paper. This level shifter has a wider voltage conversion, less transmission delay, higher energy efficiency, and more flexibility in the physical layout than those described in previous citations. The proposed level shifter can convert a 210-mV input signal into a 1.2-V output signal across process corners with a flexible physical layout when implemented in 65-nm LP technology. For a voltage of 0.2V, the circuit has a propagation delay of 19.4 ns, a static power dissipation of 1.84 nW, and an energy consumption per transition of 82.2 fJ for a 1-MHz input signal. Due to these excellent characteristics, the proposed design is particularly suitable for applications in multi-voltage digital systems.
The Deformation and Ageing of Mild Steel: III Discussion of Results

An attempt is made here to explain the observed phenomena in the yielding and ageing of mild steel, described in two previous papers, in the general terms of a grain-boundary theory. On this hypothesis, a satisfactory explanation of the variation of the lower yield point with grain size may be developed. It is shown that strain-ageing must involve two processes: a healing of the grain-boundary films, coupled with a hardening in the grains themselves. A discussion of the possible nature of the grain-boundary film is also undertaken.
Toward Live Migration of SGX-Enabled Virtual Machines

Intel Software Guard Extensions (SGX) can address the information disclosure in cloud computing. However, the existing virtual machine managers do not provide the efficient management operations of the SGX-enabled virtual machines (VMs) like live migration. In this paper, we identify challenges and propose a novel approach and its implementation model to migrate the SGX-enabled VMs. As future work, we will design the protocol and new instructions for live migration of the SGX-enabled VMs, and implement them on top of OpenSGX, an open source SGX emulator.
Endothelial dysfunction precedes hypertension in diet-induced insulin resistance.

The insulin-resistant (IR) syndrome may be an impetus for the development of hypertension (HTN). Unfortunately, the mechanism by which this could occur is unclear. Our laboratory and others have described impaired endothelium-mediated relaxation in IR, mildly hypertensive rats. The purpose of the current study is to determine if HTN is most likely a cause or result of impaired endothelial function. Sprague-Dawley rats were randomized to receive a fructose-rich diet for 3, 7, 10, 14, 18, or 28 days or were placed in a control group. The control group received rat chow. After diet treatment, animals were instrumented with arterial cannulas, and while awake and unrestrained, their blood pressure (BP) was measured. Subsequently, endothelium-mediated relaxation to acetylcholine was determined (in vitro) by measuring intraluminal diameter of phenylephrine-preconstricted mesenteric arteries (∼250 μM). Serum insulin levels were significantly elevated in all groups receiving fructose feeding compared with control, whereas there were no differences in serum glucose levels between groups. Impairment of endothelium-mediated relaxation starts by day 14 [mean percent maximal relaxation (Emax): 69 ± 10% of baseline] and becomes significant by day 18 (Emax: 52 ± 11% of baseline; P < 0.01). However, the mean BP (mmHg) does not become significantly elevated until day 28 [BP: 132 ± 1 ( day 28) vs. 116 ± 3 (control); P < 0.05]. These findings demonstrate that both IR and endothelial dysfunction occur before HTN in this model and suggest that endothelial dysfunction may be a mechanism linking insulin resistance and essential HTN.
A Telecom Perspective on the Internet of Drones: From LTE-Advanced to 5G

Drones are driving numerous and evolving use cases, and creating transformative socio-economic benefits. Drone operation needs wireless connectivity for communication between drones and ground control systems, among drones, and between drones and air traffic management systems. Mobile networks are well positioned to identify, track, and control the growing fleet of drones. The wide-area, quality, and secure connectivity provided by mobile networks can enhance the efficiency and effectiveness of drone operations beyond visual line-of-sight range. In this article, we elaborate how the drone ecosystem can benefit from mobile technologies, summarize key capabilities required by drone applications, and analyze the service requirements on mobile networks. We present field trial results collected in LTE-Advanced networks to gain insights into the capabilities of the current 4G+ networks for connected drones and share our vision on how 5G networks can further support diversified drone applications.
The Effects of JPEG and JPEG2000 Compression on Attacks using Adversarial Examples

Adversarial examples are known to have a negative effect on the performance of classifiers which have otherwise good performance on undisturbed images. These examples are generated by adding non-random noise to the testing samples in order to make classifier misclassify the given data. Adversarial attacks use these intentionally generated examples and they pose a security risk to the machine learning based systems. To be immune to such attacks, it is desirable to have a pre-processing mechanism which removes these effects causing misclassification while keeping the content of the image. JPEG and JPEG2000 are well-known image compression techniques which suppress the high-frequency content taking the human visual system into account. JPEG has been also shown to be an effective method for reducing adversarial noise. In this paper, we propose applying JPEG2000 compression as an alternative and systematically compare the classification performance of adversarial images compressed using JPEG and JPEG2000 at different target PSNR values and maximum compression levels. Our experiments show that JPEG2000 is more effective in reducing adversarial noise as it allows higher compression rates with less distortion and it does not introduce blocking artifacts.
Factors influencing P terminal force in lead V1 of the ECG in hemodialysis patients

Introduction Atrial fibrillation (AF) is a highly prevalent arrhythmia in hemodialysis (HD) patients, and an HD session may be a trigger for AF episodes. An abnormal P-terminal force in lead V1 (PTFV1) may predict new-onset AF in HD patients. The aim of the study was to assess the influence of the HD process on PTFV1 and to evaluate possible factors influencing PTFV1 in a group of selected HD patients. Material and methods One hundred and fifty-three selected HD patients entered the study. Blood chemistry, electrocardiography, and impedance cardiography were evaluated before and after HD. Echocardiography was performed on the morning after dialysis. Abnormal PTFV1 was defined as PTFV1 > 40 mm × ms. Results Abnormal PTFV1 was found in 35.3% of patients before dialysis and in 48.4% of patients after dialysis. The results of multiple regression analysis revealed that the independent predictors of pre-dialysis abnormal PTFV1 were: left atrial volume index (p = 0.002), left ventricular mass index (p = 0.014), and pre-dialysis thoracic fluid content (p = 0.021) values. The independent predictors of HD-induced abnormal PTFV1 values were larger differences between pre-dialysis and post-dialysis values of serum potassium (p < 0.001) and mean arterial pressure (p = 0.008). Conclusions Abnormal PTFV1 is prevalent in HD patients. The HD process adversely affects PTFV1 values. Pre-dialysis abnormal PTFV1 is mainly associated with structural heart abnormalities and hydration status. HD-induced abnormal PTFV1 is associated predominantly with serum potassium changes as well as HD-induced hypotension. Our results suggest possible risk factors for AF; however, their clinical significance needs to be confirmed in follow-up studies.
A multicenter, retrospective medical record review of X‐linked myotubular myopathy: The recensus study

Introduction: X‐linked myotubular myopathy (XLMTM), characterized by severe hypotonia, weakness, respiratory distress, and early mortality, is rare and natural history studies are few. Methods: RECENSUS is a multicenter chart review of male XLMTM patients characterizing disease burden and unmet medical needs. Data were collected between September 2014 and June 2016. Results: Analysis included 112 patients at six clinical sites. Most recent patient age recorded was ≤18 months for 40 patients and >18 months for 72 patients. Mean (SD) age at diagnosis was 3.7 (3.7) months and 54.3 (77.1) months, respectively. Mortality was 44% (64% ≤18 months; 32% >18 months). Premature delivery occurred in 34/110 (31%) births. Nearly all patients (90%) required respiratory support at birth. In the first year of life, patients underwent an average of 3.7 surgeries and spent 35% of the year in the hospital. Discussion: XLMTM is associated with high mortality, disease burden, and healthcare utilization. Muscle Nerve 57: 550–560, 2018
Coordination of Heparan Sulfate Proteoglycans with Wnt Signaling To Control Cellular Migrations and Positioning in Caenorhabditis elegans

Heparan sulfates (HS) are linear polysaccharides with complex modification patterns, which are covalently bound via conserved attachment sites to core proteins to form heparan sulfate proteoglycans (HSPGs). HSPGs regulate many aspects of the development and function of the nervous system, including cell migration, morphology, and network connectivity. HSPGs function as cofactors for multiple signaling pathways, including the Wnt-signaling molecules and their Frizzled receptors. To investigate the functional interactions among the HSPG and Wnt networks, we conducted genetic analyses of each, and also between these networks using five cellular migrations in the nematode Caenorhabditis elegans. We find that HSPG core proteins act genetically in a combinatorial fashion dependent on the cellular contexts. Double mutant analyses reveal distinct redundancies among HSPGs for different migration events, and different cellular migrations require distinct heparan sulfate modification patterns. Our studies reveal that the transmembrane HSPG SDN-1/Syndecan functions within the migrating cell to promote cellular migrations, while the GPI-linked LON-2/Glypican functions cell nonautonomously to establish the final cellular position. Genetic analyses with the Wnt-signaling system show that (1) a given HSPG can act with different Wnts and Frizzled receptors, and that (2) a given Wnt/Frizzled pair acts with different HSPGs in a context-dependent manner. Lastly, we find that distinct HSPG and Wnt/Frizzled combinations serve separate functions to promote cellular migration and establish position of specific neurons. Our studies suggest that HSPGs use structurally diverse glycans in coordination with Wnt-signaling pathways to control multiple cellular behaviors, including cellular and axonal migrations and, cellular positioning.
Host population structure and treatment frequency maintain balancing selection on drug resistance

It is a truism that antimicrobial drugs select for resistance, but explaining pathogen- and population-specific variation in patterns of resistance remains an open problem. Like other common commensals, Streptococcus pneumoniae has demonstrated persistent coexistence of drug-sensitive and drug-resistant strains. Theoretically, this outcome is unlikely. We modeled the dynamics of competing strains of S. pneumoniae to investigate the impact of transmission dynamics and treatment-induced selective pressures on the probability of stable coexistence. We find that the outcome of competition is extremely sensitive to structure in the host population, although coexistence can arise from age-assortative transmission models with age-varying rates of antibiotic use. Moreover, we find that the selective pressure from antibiotics arises not so much from the rate of antibiotic use per se but from the frequency of treatment: frequent antibiotic therapy disproportionately impacts the fitness of sensitive strains. This same phenomenon explains why serotypes with longer durations of carriage tend to be more resistant. These dynamics may apply to other potentially pathogenic, microbial commensals and highlight how population structure, which is often omitted from models, can have a large impact.
Cytokine response patterns to complex biofilms by mononuclear cells discriminate patient disease status and biofilm dysbiosis

ABSTRACT Localized aggressive periodontitis (LAP) is a rare form of periodontal disease with site-specific rapid tissue destruction. A lipopolysaccharide (LPS) hyper-inflammatory response was shown in LAP using peripheral whole blood, although responses to other bacterial surface components or complex oral biofilms have not been evaluated. Peripheral blood mononuclear cells (PBMCs) from 14 LAP patients, 15 healthy siblings (HS), and 13 unrelated healthy controls (HC) were stimulated with: LPS, lipoteichoic acid, or peptidoglycan; intact or sonically dispersed in vitro–grown biofilms from a LAP disease site, a LAP healthy site, or a healthy control site. Cell culture supernatants were assayed for 14 cyto/chemokines. Discriminant function analysis determined cyto/chemokines that discriminate disease status by response patterns to different stimuli. Qualitative differences in the cytokine response pattern among patient groups were observed to intact and dispersed biofilms, yet responses to healthy and diseased biofilms could not be discriminated. Despite an equivalent magnitude of response, LAP-derived PBMCs demonstrated a qualitatively different pattern of response to LPS and dispersed biofilms. PMBCs from each group responded distinctly to stimulation withsubgingival biofilms. Multiple underlying mechanisms related to bacterial-induced inflammatory responses can culminate in LAP disease initiation and/or progression, and biofilm homeostasis could play an important role.
Experience-dependent shaping of hippocampal CA1 intracellular activity in novel and familiar environments

The hippocampus is critical for producing stable representations of familiar spaces. How these representations arise is poorly understood, largely because changes to hippocampal inputs have not been measured during spatial learning. Here, using intracellular recording, we monitored inputs and plasticity-inducing complex spikes (CSs) in CA1 neurons while mice explored novel and familiar virtual environments. Inputs driving place field spiking increased in amplitude – often suddenly – during novel environment exploration. However, these increases were not sustained in familiar environments. Rather, the spatial tuning of inputs became increasingly similar across repeated traversals of the environment with experience – both within fields and throughout the whole environment. In novel environments, CSs were not necessary for place field formation. Our findings support a model in which initial inhomogeneities in inputs are amplified to produce robust place field activity, then plasticity refines this representation into one with less strongly modulated, but more stable, inputs for long-term storage. DOI: http://dx.doi. org/10.7554/eLife.23040. 001
Insights Into Vaginal Bacterial Communities and Metabolic Profiles of Chlamydia trachomatis Infection: Positioning Between Eubiosis and Dysbiosis

The vaginal microbiota plays a crucial role in maintaining the health and functioning of the female genital tract, preventing the colonization of urogenital pathogens and sexually transmitted infections. In this study, we characterized the vaginal bacterial communities and the metabolome associated to Chlamydia trachomatis infection (CT: 20 women), compared to healthy condition (H: 22 women) and bacterial vaginosis (BV: 19 women). A microarray-based tool (VaginArray), implemented with a real-time PCR for Gardnerella vaginalis, was used to determine the vaginal bacterial composition, whereas the metabolic profiles were assessed by a proton-based nuclear magnetic resonance (1H-NMR) spectroscopy. CT infection was characterized by bacterial and metabolic signatures similar to healthy condition, even though higher amounts of Lactobacillus iners, as well as depletion of some amino acids, biogenic amines, and succinate marked CT infection. Moreover, the frequency of Lactobacillus crispatus was higher in asymptomatic CT-positive patients than in women with CT-correlated symptoms. We also confirmed the marked differences in the microbiome and metabolome between healthy and BV-affected women. In conclusion, we highlighted microbial and metabolic peculiarities of the vaginal ecosystem in the case of CT infection, even though further studies are needed to understand if the observed alterations precede the infection onset or if the pathogen itself perturbs the vaginal environment.
Optimizing Propagation of Staphylococcus aureus Infecting Bacteriophage vB_SauM-phiIPLA-RODI on Staphylococcus xylosus Using Response Surface Methodology

The use of bacteriophages for killing pathogenic bacteria is a feasible alternative to antibiotics and disinfectants. To obtain the large quantities of phages required for this application, large-scale production of bacteriophages must be optimized. This study aims to define conditions that maximize the phage yield of the virulent and polyvalent staphylococcal bacteriophage vB_SauM-phiIPLA-RODI in broth culture, using the food-grade species Staphylococcus xylosus as the host strain to reduce the risk of growing massive quantities of pathogenic bacteria and therefore, to ensure the safety of the final phage stock. The effect of four variables, namely initial bacterial concentration (5.66–8.40 log10 colony-forming unit (CFU)/mL), initial phage concentration (5–8 log10 plaque-forming unit (PFU)/mL), temperature (21–40 °C) and agitation (20–250 rpm), on phage yield (response) was studied by using response surface methodology (RSM). Successive experimental designs showed that agitation did not significantly impact phage yield, while temperature did have a significant effect, with 38 °C being the optimum for phage propagation. The results allowed the design of a model to describe phage yield as a function of the initial bacterial and phage concentrations at fixed agitation (135 rpm), and optimum temperature (38 °C). The maximum experimental phage yield obtained was 9.3 log10 PFU/mL, while that predicted by the model under the optimized conditions (7.07 log10 CFU/mL initial bacterial population and 6.00 log10 PFU/mL initial phage titer) was 9.25 ± 0.30 log10 PFU/mL, with the desirability of 0.96. This yield is comparable to that obtained when the phage was propagated on the original host, Staphylococcus aureus. Bacteriophage phiIPLA-RODI showed the same host range and very similar biofilm removal ability regardless of the staphylococcal species used for its propagation. The results presented in this study show the suitability of using a food-grade strain of S. xylosus for the propagation of S. aureus infecting phages and the application of RSM to define the optimal propagation conditions.
Alterations in contractile properties and Ca2+ handling in streptozotocin-induced diabetic rat myocardium.

The mechanisms of the slower time courses of Ca2+transients (CaT) and contraction in diabetic (diabetes mellitus, DM) myocardium were studied. The aequorin method was applied to papillary muscles of streptozotocin-induced DM and control rats. The time courses of CaT and tension of twitch in DM were slower than those in control, although the magnitudes of the CaT and contraction were identical. The dependence of CaT decay time and relaxation time on developed tension in DM and control rats differed. The length-tension relation in twitch and the pCa-tension relation in tetanus were identical in the two groups. The magnitude of extra Ca2+ (transient increase in intracellular Ca2+ concentration induced by a quick release in tetanus) was identical in both groups. pCa-tension relations of skinned trabeculae at different sarcomere lengths were nearly identical. The cross-bridge cycling rate (CCR) in DM was slower than that in control. These results indicate that the tension-dependent change in the Ca2+ affinity of troponin C in DM myocardium functions as in control myocardium. The slower time courses of CaT and tension in DM myocardium are caused by slower Ca2+ uptake by the sarcoplasmic reticulum and the slower CCR.