Miracle-dz/UniFAR-FTUs huggingface dataset:
Single molecule detection of direct, homologous, DNA/DNA pairing

Using a parallel single molecule magnetic tweezers assay we demonstrate homologous pairing of two double-stranded (ds) DNA molecules in the absence of proteins, divalent metal ions, crowding agents, or free DNA ends. Pairing is accurate and rapid under physiological conditions of temperature and monovalent salt, even at DNA molecule concentrations orders of magnitude below those found in vivo, and in the presence of a large excess of nonspecific competitor DNA. Crowding agents further increase the reaction rate. Pairing is readily detected between regions of homology of 5 kb or more. Detected pairs are stable against thermal forces and shear forces up to 10 pN. These results strongly suggest that direct recognition of homology between chemically intact B-DNA molecules should be possible in vivo. The robustness of the observed signal raises the possibility that pairing might even be the “default” option, limited to desired situations by specific features. Protein-independent homologous pairing of intact dsDNA has been predicted theoretically, but further studies are needed to determine whether existing theories fit sequence length, temperature, and salt dependencies described here.
Posture recognition analysis during human-robot imitation learning

Imitation is a powerful paradigm for learning new actions and tasks and is currently investigated in several research domains such as developmental psychology or robotics [8]. For example, learning by demonstration is employed in robotics to teach new skills and tasks to robots [1] [2]. The dynamics of coupling of perception of one partner to the action of the other, and vice-and-versa, has been exploited to characterize social traits [9]. In particular, in the case of strong coupling such as imitation, research in developmental science has shown that imitation could be considered a social referencing mechanism [7]. Recently, identification of social traits during human-robot imitation learning has been successfully demonstrated. For example a social signature emerges from a neural network architecture and distinguishes typical children and children with Autism Spectrum Disorders (ASD). The key idea of this approach is to learn the mapping between the perception of postures performed by the children and the actions performed by the robot. A perception-action architecture based on neural network (PerAc [6]) is used to associate the perception with action [3]. Interestingly, this approach generalizes to person's identity recognition by the analysis of the dynamics of the social signature (novelty detection procedure) [5].
Interference suppression through power allocation for massive MIMO systems with channel aging

To acquire an optimum potential of massive multiple-input multiple-output (MIMO), congruity between pre-coder and the actual channel is required. This circumstance, however, is hard to obtain when the mobile station (MS) is moving in a multipath environment and experiencing channel aging. Suffering channel aging, a mismatch between the precoder matrix and the actual channel matrix occurs which causes interuser interference at the MS. To tackle this problem, we propose a channel prediction based power allocation technique for time-varying massive MIMO. First, we estimate Doppler shift experienced by the BS to create a channel prediction. Afterward, we conduct recursive power allocation with the goal of minimizing channel aging effect at the MS. Using the proposed technique, each MS only suffers a certain interference level which still can be handled by the MS. Through computer simulation, it is shown that our proposed technique enables the time-varying massive MIMO transmission without a significant addition to computational complexity.
Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases

Silent Information Regulator 2 (Sir2) enzymes (or sirtuins) are NAD+-dependent deacetylases that modulate gene silencing, aging and energy metabolism. Previous work has implicated several transcription factors as sirtuin targets. Here, we investigated whether mammalian sirtuins could directly control the activity of metabolic enzymes. We demonstrate that mammalian Acetyl-CoA synthetases (AceCSs) are regulated by reversible acetylation and that sirtuins activate AceCSs by deacetylation. Site-specific acetylation of mouse AceCS1 on Lys-661 was identified by using mass spectrometry and a specific anti-acetyl-AceCS antibody. SIRT1 was the only member of seven human Sir2 homologues capable of deacetylating AceCS1 in cellular coexpression experiments. SIRT1 expression also led to a pronounced increase in AceCS1-dependent fatty-acid synthesis from acetate. Using purified enzymes, only SIRT1 and SIRT3 exhibited high catalytic efficiency against acetylated AceCS1. In mammals, two AceCSs have been identified: cytoplasmic AceCS1 and mitochondrial AceCS2. Because SIRT3 is localized to the mitochondria, we investigated whether AceCS2 also might be regulated by acetylation, and specifically deacetylated by mitochondrial SIRT3. AceCS2 was completely inactivated upon acetylation and was rapidly reactivated by SIRT3 deacetylation. Lys-635 of mouse AceCS2 was identified as the targeted residue. Using reversible acetylation to modulate enzyme activity, we propose a model for the control of AceCS1 by SIRT1 and of AceCS2 by SIRT3.
White matter lesion burden in migraine with aura may be associated with reduced cerebral blood flow

Objective The objective of this study was to determine whether white matter hyperintensities (WMHs) in subjects with migraine are related to alterations in resting cerebral blood flow (CBF). Methods Migraine with aura (MWA), migraine without aura (MwoA), and control subjects were enrolled in a 1:1:1 ratio. WMH load was scored based on fluid-attenuated inversion recovery/T2-weighted magnetic resonance imaging (MRI) using a previously established semi-quantitative scale. Global and regional CBFs were quantified using arterial spin labelled perfusion MRI. Integrity of the circle of Willis was assessed with magnetic resonance angiography (MRA). Results A total of 170 subjects were enrolled (54 controls, 56 MWA, and 60 MwoA). There was no significant difference in subjects with ≥1 WMH across groups (22% controls, 29% MWA, 35% MwoA; p = NS). Similarly, high WMH load was not significantly different across groups (16.7% controls, 21.4% MWA, 25.0% MwoA; p = NS). High WMH load was strongly associated with increasing age (odds ratio: 1.08 per year, 95% confidence interval: 1.02–1.13, p = 0.01). Resting CBF was similar across groups, but was significantly higher in women. In MWA subjects with high WMH load, CBF was substantially lower (p = 0.03). No association between WMH load and CBF was seen in control or MwoA subjects. Conclusions WHMs in MWA may be related to alterations in resting CBF.
Mild Hypokalemia and Supraventricular Ectopy Increases the Risk of Stroke in Community-Dwelling Subjects

Background and Purpose— Stroke is independently associated with the common conditions of hypokalemia and supraventricular ectopy, and we hypothesize that the combination of excessive supraventricular ectopic activity and hypokalemia has a synergistic impact on the prognosis in terms of stroke in the general population. Methods— Subjects (55–75 years old) from the Copenhagen Holter Study cohort (N=671) with no history of atrial fibrillation or stroke were studied—including baseline values of potassium and ambulatory 48-hour Holter monitoring. Excessive supraventricular ectopic activity is defined as ≥30 premature atrial complexes per hour or any episodes of runs of ≥20. Hypokalemia was defined as plasma-potassium ⩽3.6 mmol/L. The primary end point was ischemic stroke. Cox models were used. Results— Hypokalemia was mild (mean, 3.4 mmol/L; range, 2.7–3.6). Hypokalemic subjects were older (67.0±6.94 versus 64.0±6.66 years; P<0.0001) and more hypertensive (165.1±26.1 versus 154.6±23.5 mm Hg; P<0.0001). Median follow-up time was 14.4 years (Q1–Q3, 9.4–14.7 years). The incidence of stroke was significantly higher in the hypokalemic group (hazard ratio, 1.84; 95% confidence interval, 1.04–3.28) after covariate adjustments, as well as in a competing risk analysis with death (hazard ratio, 1.51; 95% confidence interval, 1.12–2.04). Excessive supraventricular ectopic activity was also associated with stroke (hazard ratio, 2.23; 95% confidence interval, 1.33–3.76). The combination of hypokalemia and excessive supraventricular ectopic activity increased the risk of events synergistically. Stroke rate was 93 per 1000 patient-year (P<0.0001) in this group (n=17) compared with 6.9 (n=480); 11 (n=81), and 13 (n=93) per 1000 patient-year in the groups without the combination. Conclusions— The combination of hypokalemia and excessive supraventricular ectopy carries a poor prognosis in terms of stroke.
Outsmarting Network Security with SDN Teleportation

Software-defined networking is considered a promising new paradigm, enabling more reliable and formally verifiable communication networks. However, this paper shows that the separation of the control plane from the data plane, which lies at the heart of Software-Defined Networks (SDNs), introduces a new vulnerability which we call teleportation. An attacker (e.g., a malicious switch in the data plane or a host connected to the network) can use teleportation to transmit information via the control plane and bypass critical network functions in the data plane (e.g., a firewall), and to violate security policies as well as logical and even physical separations. This paper characterizes the design space for teleportation attacks theoretically, and then identifies four different teleportation techniques. We demonstrate and discuss how these techniques can be exploited for different attacks (e.g., exfiltrating confidential data at high rates), and also initiate the discussion of possible countermeasures. Generally, and given today's trend toward more intent-based networking, we believe that our findings are relevant beyond the use cases considered in this paper.
Alternative Translation Initiation of a Haloarchaeal Serine Protease Transcript Containing Two In-Frame Start Codons

ABSTRACT Recent studies have shown that haloarchaea employ leaderless and Shine-Dalgarno (SD)-less mechanisms for translation initiation of leaderless transcripts with a 5′ untranslated region (5′ UTR) of <10 nucleotides (nt) and leadered transcripts with a 5′ UTR of ≥10 nt, respectively. However, whether the two mechanisms can operate on the same naturally occurring haloarchaeal transcript carrying multiple potential start codons is unknown. In this study, the transcript of the sptA gene (encoding an extracellular serine protease of Natrinema sp. strain J7-2) was experimentally determined and found to contain two potential in-frame AUG codons (AUG1 and AUG2) located 5 and 29 nt, respectively, downstream of the transcription start site. Mutational analysis revealed that both AUGs can function as the translation start codon for production of active SptA, although AUG1 is more efficient than AUG2 for translation initiation. Insertion of a stable stem-loop structure between the two AUGs completely abolished initiation at AUG1 but did not affect initiation at AUG2, indicating that AUG2-initiated translation does not involve ribosome scanning from the 5′ end of the transcript. Furthermore, the efficiency of AUG2-initiated translation was not influenced by an upstream SD-like sequence. In addition, both AUG1 and AUG2 contribute to transcript stability, probably by recruiting ribosomes to protect the transcript against degradation. These data suggest that depending on which of two in-frame start codons is used, the sptA transcript can act as either a leaderless or a leadered transcript for SptA production in haloarchaea. IMPORTANCE In eukaryotes and bacteria, alternative translation start sites contribute to proteome complexity and can be used as a functional mechanism to increase translation efficiency. However, little is known about alternative translation initiation in archaea. Our results demonstrate that leaderless and SD-less mechanisms can be used for translation initiation of the sptA transcript from two in-frame start codons, raising the possibility that in haloarchaea, alternative translation initiation on one transcript functions to increase translation efficiency and/or contribute to proteome complexity.
Embedded silicon detector to investigate the natural radiative environment

A detector based on a silicon diode was developed to investigate the natural radiative environment. As the detector is embeddable, it has low power consumption and is lightweight and small. The instrument was tested under different neutron beams and used during stratospheric balloon flights. A comparison of the experimental results with Monte Carlo simulation results shows that the embeddable detector is a promising means of investigating the natural radiative environment.
MyoScreen, a High-Throughput Phenotypic Screening Platform Enabling Muscle Drug Discovery

Despite the need for more effective drug treatments to address muscle atrophy and disease, physiologically accurate in vitro screening models and higher information content preclinical assays that aid in the discovery and development of novel therapies are lacking. To this end, MyoScreen was developed: a robust and versatile high-throughput high-content screening (HT/HCS) platform that integrates a physiologically and pharmacologically relevant micropatterned human primary skeletal muscle model with a panel of pertinent phenotypic and functional assays. MyoScreen myotubes form aligned, striated myofibers, and they show nerve-independent accumulation of acetylcholine receptors (AChRs), excitation–contraction coupling (ECC) properties characteristic of adult skeletal muscle and contraction in response to chemical stimulation. Reproducibility and sensitivity of the fully automated MyoScreen platform are highlighted in assays that quantitatively measure myogenesis, hypertrophy and atrophy, AChR clusterization, and intracellular calcium release dynamics, as well as integrating contractility data. A primary screen of 2560 compounds to identify stimulators of myofiber regeneration and repair, followed by further biological characterization of two hits, validates MyoScreen for the discovery and testing of novel therapeutics. MyoScreen is an improvement of current in vitro muscle models, enabling a more predictive screening strategy for preclinical selection of the most efficacious new chemical entities earlier in the discovery pipeline process.
Disruptions of working memory and inhibition mediate the association between exposure to institutionalization and symptoms of attention deficit hyperactivity disorder

Background Young children raised in institutions are exposed to extreme psychosocial deprivation that is associated with elevated risk for psychopathology and other adverse developmental outcomes. The prevalence of attention deficit hyperactivity disorder (ADHD) is particularly high in previously institutionalized children, yet the mechanisms underlying this association are poorly understood. We investigated whether deficits in executive functioning (EF) explain the link between institutionalization and ADHD. Method A sample of 136 children (aged 6–30 months) was recruited from institutions in Bucharest, Romania, and 72 never institutionalized community children matched for age and gender were recruited through general practitioners’ offices. At 8 years of age, children's performance on a number of EF components (working memory, response inhibition and planning) was evaluated. Teachers completed the Health and Behavior Questionnaire, which assesses two core features of ADHD, inattention and impulsivity. Results Children with history of institutionalization had higher inattention and impulsivity than community controls, and exhibited worse performance on working memory, response inhibition and planning tasks. Lower performances on working memory and response inhibition, but not planning, partially mediated the association between early institutionalization and inattention and impulsivity symptom scales at age 8 years. Conclusions Institutionalization was associated with decreased EF performance and increased ADHD symptoms. Deficits in working memory and response inhibition were specific mechanisms leading to ADHD in previously institutionalized children. These findings suggest that interventions that foster the development of EF might reduce risk for psychiatric problems in children exposed to early deprivation.
Early life risk exposure and stunting in urban South African 2-year old children

Stunting is a measure of overall nutritional status and is a major public health concern because of its association with child mortality and morbidity and later adult performance. This study examined the effects of pregnancy events, birth characteristics and infant risk exposure on stunting at age 2 years. The study, established in 1990 in Soweto, an urban South African township, included 1098 mother–infant pairs enroled in the Birth to Twenty Plus longitudinal birth cohort study. In total, 22% of children were stunted at age 2 years, with males at greater risk than females [24.8 v. 19.4%, odds ratio (OR)=1.38; 95% confidence interval (CI): 1.03, 1.83]. In unadjusted analysis, male sex, household socio-economic status (SES), overcrowding, maternal age, maternal education, single motherhood, ethnicity, birth weight, gestational age and duration of infant breastfeeding were all significantly associated with stunting. In multivariable analysis, higher birth weight was protective against stunting for both sexes. Higher maternal education was protective for females only (adjusted odds ratio (AOR)=0.35; 95% CI: 0.14, 0.87), whereas wealthier household SES protected males (AOR for richest SES group=0.39; 95% CI: 0.16, 0.92). In this and other similar settings, current stunting prevention efforts focussing on primarily providing targeted proximal interventions, such as food supplements, risk undermining the critical importance of addressing key distal determinants of stunting such as SES and maternal education.
Association of Ideal Cardiovascular Health With Vascular Brain Injury and Incident Dementia

Background and Purpose— The American Heart Association developed the ideal cardiovascular health (CVH) index as a simple tool to promote CVH; yet, its association with brain atrophy and dementia remains unexamined. Methods— Our aim was to investigate the prospective association of ideal CVH with vascular brain injury, including the 10-year risks of incident stroke and dementia, as well as cognitive decline and brain atrophy on magnetic resonance imaging, measured for ≈7 years. We studied 2750 stroke- and dementia-free Framingham Heart Study Offspring cohort participants (mean age, 62±9 years; 45% men). Ideal CVH was quantified on a 7-point scale with 1 point awarded for each of the following: nonsmoking status, ideal body mass index, regular physical activity, healthy diet, as well as optimum blood pressure, cholesterol, and fasting blood glucose. Both recent (baseline) and remote (6.9 years earlier) ideal CVH scores were examined. Results— Recent ideal CVH was associated with stroke (hazard ratio, 0.80; 95% confidence interval, 0.67–0.95), vascular dementia (hazard ratio, 0.49; 95% confidence interval, 0.30–0.81), frontal brain atrophy (P=0.003), and cognitive decline on tasks measuring visual memory and reasoning (P<0.05). In addition to predicting stroke, vascular dementia, whole-brain atrophy, and cognitive decline, remote ideal CVH was associated with the incidence of all-cause dementia (hazard ratio, 0.80; 95% confidence interval, 0.67–0.97) and Alzheimer disease (hazard ratio, 0.79; 95% confidence interval, 0.64–0.98). Conclusions— Adherence to the American Heart Association’s ideal CVH factors and behaviors, particularly in midlife, may protect against cerebrovascular disease and dementia.
Digital Predistortion for Multi-Antenna Transmitters Affected by Antenna Crosstalk

In this paper, a digital predistortion (DPD) technique for wideband multi-antenna transmitters is proposed. The proposed DPD compensates for the combined effects of power amplifier (PA) nonlinearity, antenna crosstalk, and impedance mismatch. The proposed technique consists of a linear crosstalk and mismatch model block shared by all transmit paths and a dual-input DPD block in every transmit path. By avoiding the use of multi-input DPD blocks in every transmit path, the complexity of the proposed technique is kept low and scales more favorably with the number of antennas than competing techniques. It is shown that all blocks can be identified from measurements of the PA output signals using least-squares estimation. Measurement results of a four-path transmitter are presented and used to evaluate the proposed DPD technique against existing techniques. The results show that the performance of the proposed DPD technique is similar to those of existing techniques, while the complexity is lower.
Mechanisms of organelle biogenesis govern stochastic fluctuations in organelle abundance

Fluctuations in organelle abundance can profoundly limit the precision of cell biological processes from secretion to metabolism. We modeled the dynamics of organelle biogenesis and predicted that organelle abundance fluctuations depend strongly on the specific mechanisms that increase or decrease the number of a given organelle. Our model exactly predicts the size of experimentally measured Golgi apparatus and vacuole abundance fluctuations, suggesting that cells tolerate the maximum level of variability generated by the Golgi and vacuole biogenesis pathways. We observe large increases in peroxisome abundance fluctuations when cells are transferred from glucose-rich to fatty acid-rich environments. These increased fluctuations are significantly diminished in mutants lacking peroxisome fission factors, leading us to infer that peroxisome biogenesis switches from de novo synthesis to primarily fission. Our work provides a general framework for exploring stochastic organelle biogenesis and using fluctuations to quantitatively unravel the biophysical pathways that control the abundance of subcellular structures. DOI: http://dx.doi. org/10.7554/eLife.02678. 001