Miracle-dz/UniFAR-FTUs huggingface dataset:
Low density lattice codes for the relay channel

We study practical, efficient codes for the Gaussian relay channel. It has been demonstrated that low-density lattice codes (LDLCs) can provide near-capacity performance for point-to-point Gaussian channels. We present an LDLC formulation that provides performance near the decode-and-forward inner bound of the relay channel capacity. We employ a superposition block Markov strategy tailored to LDLCs and design an appropriate iterative decoder. We characterize the error performance via simulations, showing that our scheme achieves performance only 2dB away from the decode-and-forward bound.
Small-molecule inhibitors reveal multiple strategies for Hedgehog pathway blockade

Inappropriate activation of the Hedgehog (Hh) signaling pathway has been implicated in a diverse spectrum of cancers, and its pharmacological blockade has emerged as an anti-tumor strategy. While nearly all known Hh pathway antagonists target the transmembrane protein Smoothened (Smo), small molecules that suppress downstream effectors could more comprehensively remediate Hh pathway-dependent tumors. We report here four Hh pathway antagonists that are epistatic to the nucleocytoplasmic regulator Suppressor of Fused [Su(fu)], including two that can inhibit Hh target gene expression induced by overexpression of the Gli transcription factors. Each inhibitor has a unique mechanism of action, and their phenotypes reveal that Gli processing, Gli activation, and primary cilia formation are pharmacologically targetable. We further establish the ability of certain compounds to block the proliferation of cerebellar granule neuron precursors expressing an oncogenic form of Smo, and we demonstrate that Hh pathway inhibitors can have tissue-specific activities. These antagonists therefore constitute a valuable set of chemical tools for interrogating downstream Hh signaling mechanisms and for developing chemotherapies against Hh pathway-related cancers.
Parabromophenacyl Bromide Inhibits Subepithelial Fibrosis by Reducing TGF-β1 in a Chronic Mouse Model of Allergic Asthma

Background: Our previous study showed that parabromophenacyl bromide (PBPB) inhibits the features of allergic airway inflammation and airway hyperresponsiveness (AHR). However, its effect on airway remodeling, e.g. subepithelial ﬁbrosis in a chronic allergic asthma model, was not investigated. We examined this issue in this study. Methods: PBPB was administered to mice with an induced chronic asthmatic condition. AHR was estimated at the end of the experiment, followed by euthanasia. Lung sections were stained with hematoxylin and eosin, periodic acid-Schiff and Masson's trichrome to determine airway inflammation, goblet cell metaplasia and subepithelial fibrosis, respectively. Transforming growth factor-β1 (TGF-β1) was estimated in lung homogenates. To determine the effect of PBPB on smooth-muscle hyperplasia, immunohistochemistry against α-smooth-muscle actin was performed on the lung sections. Results: Chronic ovalbumin challenges in a mouse model of allergic asthma caused significant subepithelial ﬁbrosis and elevated TGF-β1, along with significant AHR. PBPB attenuated subepithelial ﬁbrosis with a reduction of lung TGF-β1, airway inflammation and AHR without affecting goblet cell metaplasia. It also attenuated smooth-muscle hyperplasia with a reduction in the expression of α-smooth-muscle actin in the lungs. Conclusion: Our findings indicate that PBPB attenuates some crucial features of airway remodeling such as subepithelial ﬁbrosis and smooth-muscle hyperplasia. These data suggest that PBPB could therefore be a therapeutic drug for chronic asthma.
Depression and recovery of transmission at the squid giant synapse.

1. The process of synaptic depression and recovery were studied in the squid (Loligo pealii) giant synapse with intracellular recording and stimulating electrodes in the prescence of tetrodotoxin (10‐minus 7 M). 2. When the synapse was stimulated at 50 Hz, depression occurred rapidly. Recovery after the tetanus was a first‐order process with an average recovery time constant of 4‐9 sec. The rate of recovery was independent of the amplitude of the post‐synaptic potential (p.s.p.) or the degree of depression. 3. For the first five to seven p.s. p.s in the train there was a linear relationship between depression and the total amount of transmitter previously released. This may indicate that depression in this preparation was caused by the depletion of the presynaptic store of transmitter (S). 4. Assuming that this interpretation was correct, we could show that recovery from depression during the tetanus (i.e. ‘mobilization’) proceeded about 10 times faster than after the end of the tetanus. 5. When the amplitude of the p.s. p. was varied by changing the bathing calcium concentration, [Ca], the degree of depression was correlated to the amplitude of the p.s. p. 6. When the amplitude of the p.s. p. was increased by increasing pre‐synaptic depolarization, synaptic depression was found to increase as well. However, synaptic depression increased less than the amplitude of the p.s. p., the relationship between these two measures being non‐linear. 7. This finding is interpreted to indicate that the transmitter stores, S, are closely related to the area of the presynaptic membrane which is sufficiently depolarized to release transmitter.
Colonic polyp segmentation in CT colonography-based on fuzzy clustering and deformable models

An automatic method to segment colonic polyps in computed tomography (CT) colonography is presented in this paper. The method is based on a combination of knowledge-guided intensity adjustment, fuzzy c-mean clustering, and deformable models. The computer segmentations were compared with manual segmentations to validate the accuracy of our method. An average 76.3% volume overlap percentage among 105 polyp detections was reported in the validation, which was very good considering the small polyp size. Several experiments were performed to investigate the intraoperator and interoperator repeatability of manual colonic polyp segmentation. The investigation demonstrated that the computer-human repeatability was as good as the interoperator repeatability. The polyp segmentation was also applied in computer-aided detection (CAD) to reduce the number of false positive (FP) detections and provide volumetric features for polyp classification. Our segmentation method was able to eliminate 30% of FP detections. The volumetric features computed from the segmentation can further reduce FP detections by 50% at 80% sensitivity.
A model of acoustic transmission in the respiratory system

A theoretical model of sound transmission from within the respiratory tract to the chest wall due to the motion of the walls of the large airways is developed. The vocal tract, trachea, and first five bronchial generations are represented over the frequency range from 100 to 600 Hz by an equivalent acoustic circuit. This circuit makes it possible to estimate the magnitude of airway wall motion in response to an acoustic perturbation at the month. The radiation of sound through the surrounding lung parenchyma is represented as a cylindrical wave in a homogeneous mixture of air bubbles in water. The effect of thermal losses associated with the polytropic compressions and expansions of these bubbles by the acoustic wave is included, and the chest wall is represented as a massive boundary to the wave propagation. The model estimates the magnitude of acceleration over the extrathoracic trachea and at three locations on the posterior chest wall in the same vertical plane. The predicted spectral characteristics of transmission are consistent with previous experimental observations. <<ETX>>
A New Algorithm for Singleton Arc Consistency

Constraint satisfaction technology emerged from AI research. Its practical success is based on integration of sophisticated search with consistency techniques reducing the search space by removing as many as possible inconsistent values from the problem. Singleton consistency is a meta-consistency technique that reinforces other pure consistency techniques by their repeated invocation and thus it achieves even better domain pruning. The paper presents a new algorithm for singleton arc consistency that improves practical time efficiency of singleton arc consistency by applying the principles behind AC-4.
MINOR QUANTITATIVE TRAIT LOCI UNDERLIE FLORAL TRAITS ASSOCIATED WITH MATING SYSTEM DIVERGENCE IN MIMULUS

Abstract The genetic basis of species differences provides insight into the mode and tempo of phenotypic divergence. We investigate the genetic basis of floral differences between two closely related plant taxa with highly divergent mating systems, Mimulus guttatus (large-flowered outcrosser) and M. nasutus (small-flowered selfer). We had previously constructed a framework genetic linkage map of the hybrid genome containing 174 markers spanning approximately 1800 cM on 14 linkage groups. In this study, we analyze the genetics of 16 floral, reproductive, and vegetative characters measured in a large segregating M. nasutus × M. guttatus F2 population (N = 526) and in replicates of the parental lines and F1 hybrids. Phenotypic analyses reveal strong genetic correlations among floral traits and epistatic breakdown of male and female fertility traits in the F2 hybrids. We use multitrait composite interval mapping to jointly locate and characterize quantitative trait loci (QTLs) underlying interspecific differences in seven floral traits. We identified 24 floral QTLs, most of which affected multiple traits. The large number of QTLs affecting each trait (mean = 13, range = 11–15) indicates a strikingly polygenic basis for floral divergence in this system. In general, QTL effects are small relative to both interspecific differences and environmental variation within genotypes, ruling out QTLs of major effect as contributors to floral divergence between M. guttatus and M. nasutus. QTLs show no pattern of directional dominance. Floral characters associated with pollinator attraction (corolla width) and self-pollen deposition (stigma-anther distance) share several pleiotropic or linked QTLs, but unshared QTLs may have allowed selfing to evolve independently from flower size. We discuss the polygenic nature of divergence between M. nasutus and M. guttatus in light of theoretical work on the evolution of selfing, genetics of adaptation, and maintenance of variation within populations.
Intracranial pressure, its components and cerebrospinal fluid pressure–volume compensation

Clinical measurement of intracranial pressure (ICP) is often performed to aid diagnosis of hydrocephalus. This review discusses analysis of ICP and its components' for the investigation of cerebrospinal fluid (CSF) dynamics. The role of pulse, slow and respiratory waveforms of ICP in diagnosis, prognostication and management of hydrocephalus is presented. Two methods related to ICP measurement are listed: an overnight monitoring of ICP and a constant‐rate infusion study. Due to the dynamic nature of ICP, a ‘snapshot’ manometric measurement of ICP is of limited use as it might lead to unreliable results. Therefore, monitoring of ICP over longer time combined with analysis of its waveforms provides more detailed information on the state of pressure–volume compensation. The infusion study implements ICP signal processing and CSF circulation model analysis in order to assess the cerebrospinal dynamics variables, such as CSF outflow resistance, compliance of CSF space, pressure amplitude, reference pressure, and CSF formation. These parameters act as an aid tool in diagnosis and prognostication of hydrocephalus and can be helpful in the assessment of a shunt malfunction.
Supervised accelerometry analysis can identify prey capture by penguins at sea

Determining where, when and how much animals eat is fundamental to understanding their ecology. We developed a technique to identify a prey capture signature for little penguins from accelerometry, in order to quantify food intake remotely. We categorised behaviour of captive penguins from HD video and matched this to time-series data from back-mounted accelerometers. We then trained a support vector machine (SVM) to classify the penguins' behaviour at 0.3 s intervals as either ‘prey handling’ or ‘swimming’. We applied this model to accelerometer data collected from foraging wild penguins to identify prey capture events. We compared prey capture and non-prey capture dives to test the model predictions against foraging theory. The SVM had an accuracy of 84.95±0.26% (mean ± s.e.) and a false positive rate of 9.82±0.24% when tested on unseen captive data. For wild data, we defined three independent, consecutive prey handling observations as representing true prey capture, with a false positive rate of 0.09%. Dives with prey captures had longer duration and bottom times, were deeper, had faster ascent rates, and had more ‘wiggles’ and ‘dashes’ (proxies for prey encounter used in other studies). The mean (±s.e.) number of prey captures per foraging trip was 446.6±66.28. By recording the behaviour of captive animals on HD video and using a supervised machine learning approach, we show that accelerometry signatures can classify the behaviour of wild animals at unprecedentedly fine scales.
Relationships of heart rate and heart rate variability with conventional and ambulatory blood pressure in the population

Background Most studies on relationships between blood pressure and autonomic nervous function, assessed by power spectral analysis of heart rate variability, have used conventional or clinic blood pressure measurements in selected subjects, which may have influenced the results. Objective We aimed to investigate, in a population-based approach, associations of heart rate and heart rate variability, assessed in basal resting conditions and in response to standing, with conventional blood pressure measured by an investigator, and with ambulatory blood pressure monitored outside the laboratory. Methods RR interval and respiration were registered in 614 men and women, ages 25–89 years. After exclusion of subjects with myocardial infarction or diabetes and elimination of unsatisfactory recordings, 549 subjects remained for analyses at supine rest and 515 of these to assess the orthostatic responses. Hypertension was present in 39% of the subjects. The low-frequency (LF) and high-frequency (HF) components of heart rate variability were quantified by use of autoregressive modelling and expressed in absolute and normalized units. Results At supine rest, indices of heart rate variability were not independently related to 24 h systolic blood pressure, whereas some indices showed weak associations with diastolic 24 h pressure; the relationships were in general stronger for conventional blood pressure. For example, partial correlation coefficients of the relationships of the LF : HF ratio with systolic pressure were 0.12 (P ⩽ 0.01) for conventional pressure and 0.02 (NS) for 24 h pressure; these coefficients amounted to 0.20 (P ⩽ 0.001) and 0.11 (P⩽ 0.01) for the diastolic pressures. The decrease of HF power and the increase of the LF : HF ratio on standing were significantly blunted at higher blood pressure, both when measured conventionally and by ambulatory monitoring (P ⩽ 0.001 for the LF : HF ratio). Conclusions Relationships between autonomic nervous function at rest, assessed by use of power spectral analysis of heart rate variability, and conventional blood pressure, can at least partly be ascribed to the influence of the measurement conditions, whereas the orthostatic autonomic responses appear to be influenced by blood pressure per se.
A national evaluation of the effect of trauma-center care on mortality.

BACKGROUND Hospitals have difficulty justifying the expense of maintaining trauma centers without strong evidence of their effectiveness. To address this gap, we examined differences in mortality between level 1 trauma centers and hospitals without a trauma center (non-trauma centers). METHODS Mortality outcomes were compared among patients treated in 18 hospitals with a level 1 trauma center and 51 hospitals non-trauma centers located in 14 states. Patients 18 to 84 years old with a moderate-to-severe injury were eligible. Complete data were obtained for 1104 patients who died in the hospital and 4087 patients who were discharged alive. We used propensity-score weighting to adjust for observable differences between patients treated at trauma centers and those treated at non-trauma centers. RESULTS After adjustment for differences in the case mix, the in-hospital mortality rate was significantly lower at trauma centers than at non-trauma centers (7.6 percent vs. 9.5 percent; relative risk, 0.80; 95 percent confidence interval, 0.66 to 0.98), as was the one-year mortality rate (10.4 percent vs. 13.8 percent; relative risk, 0.75; 95 percent confidence interval, 0.60 to 0.95). The effects of treatment at a trauma center varied according to the severity of injury, with evidence to suggest that differences in mortality rates were primarily confined to patients with more severe injuries. CONCLUSIONS Our findings show that the risk of death is significantly lower when care is provided in a trauma center than in a non-trauma center and argue for continued efforts at regionalization.
The immediate future for the medical treatment of atrial fibrillation

Atrial fibrillation is the most commonly sustained cardiac arrhythmia and a common reason for mortality and morbidity. Atrial fibrillation causes disease for three reasons: i) the ventricular rate is often high, which leads to symptoms ranging from discomfort to life threatening heart failure; ii) the rhythm causes loss of atrioventricular synchrony, which reduces diastolic filling and may lead to heart failure; and iii) atrial contraction is lost leading to stagnant blood that again may lead to atrial thrombi and peripheral embolism. Thus, the treatment of atrial fibrillation is focused on the maintenance of sinus rhythm, rate control and prevention of embolism. For the maintenance of sinus rhythm, all drugs under current development are potassium channel blockers; the so-called class III anti-arrhythmic drugs. Those which have been further investigated appear to be valuable for maintenance of sinus rhythm but all carry a significant risk of pro-arrhythmia, in particular Torsade de Pointe ventricular tachycardia. Rate control has been a focus of treatment for many years and several very old drugs, including digoxin, are used for this. There is, to the author’s knowledge, no current effort for evaluating new drugs for this indication. Prevention of embolism has for many years been obtained with vitamin K antagonists for which the clinical evidence is overwhelming. Previous attempts to replace vitamin K antagonists with aspirin have not been fruitful. A large number of newer anticoagulation regimes are in development, but to the author’s knowledge only a single thrombin inhibitor is actively being developed for atrial fibrillation.
Prominent role of KCa3.1 in endothelium-derived hyperpolarizing factor-type dilations and conducted responses in the microcirculation in vivo.

AIMS The activation of endothelial Ca2+-dependent K+-channels, KCa3.1 (IKCa), and KCa2.3 (SKCa) has been proposed to be a prerequisite for endothelial hyperpolarization, which subsequently hyperpolarizes and relaxes smooth muscle [endothelium-derived hyperpolarizing factor (EDHF)-type dilation] and initiates conducted dilations. Although EDHF is the main mediator of acetylcholine (ACh)-induced dilation in the murine skeletal microcirculation, the differential contribution of KCa3.1 and KCa2.3 is not known. METHODS AND RESULTS We assessed agonist-induced and conducted dilations as well as endothelial hyperpolarization in the cremaster microcirculation of KCa3.1-deficient (KCa3.1-/-) and wild-type mice (wt) in vivo after blockade of NO and prostaglandins. Compared with wt, resting tone was enhanced by approximately 25% in arterioles of KCa3.1-/- mice. ACh-induced dilations in KCa3.1-/- mice were virtually abolished at low and intermediate concentrations and a remaining dilation at 10 micromol/L ACh was abrogated by blockade of KCa2.3 with UCL1684. Sodium nitroprusside- and adenosine-induced dilations were similar in wt and KCa3.1-/-. Focal application of ACh induced dilations at the local site in both genotypes, which conducted along the vessel. However, the amplitude of the dilation decreased with distance only in KCa3.1-/-. Blockade of KCa2.3 in wt did not affect conducted dilations. A KCa3.1 opener induced a conducting dilation in wt but not in KCa3.1-/-. Membrane potential recordings in vivo demonstrated endothelial hyperpolarization in response to ACh in both genotypes; however, the hyperpolarization was severely impaired in KCa3.1-/- (Delta membrane potential: -3 +/- 1 vs. -14 +/- 2 mV). CONCLUSION We conclude that KCa3.1 is of major importance for endothelial hyperpolarization and EDHF-type responses in skeletal muscle arterioles, and its deficiency is not compensated by KCa2.3. Sole activation of KCa3.1 is capable of initiating conducted responses, and KCa3.1 may contribute to the propagation of the signal, although its presence is not mandatory.
Large-scale modulation of thermodynamic protein folding barriers linked to electrostatics

Protein folding barriers, which range from zero to the tens of RT that result in classical two-state kinetics, are primarily determined by protein size and structural topology [Plaxco KW, Simons KT, Baker D (1998) J Mol Biol 277:985–994]. Here, we investigate the thermodynamic folding barriers of two relatively large proteins of the same size and topology: bovine α-lactalbumin (BLA) and hen-egg-white lysozyme (HEWL). From the analysis of differential scanning calorimetry experiments with the variable-barrier model [Muñoz V, Sanchez-Ruiz JM (2004) Proc Natl Acad Sci USA 101:17646–17651] we obtain a high barrier for HEWL and a marginal folding barrier for BLA. These results demonstrate a remarkable tuning range of at least 30 kJ/mol (i.e., five to six orders of magnitude in population) within a unique protein scaffold. Experimental and theoretical analyses on these proteins indicate that the surprisingly small thermodynamic folding barrier of BLA arises from the stabilization of partially unfolded conformations by electrostatic interactions. Interestingly, there is clear reciprocity between the barrier height and the biological function of the two proteins, suggesting that the marginal barrier of BLA is a product of natural selection. Electrostatic surface interactions thus emerge as a mechanism for the modulation of folding barriers in response to special functional requirements within a given structural fold.
A Faster Distributed Radio Broadcast Primitive: Extended Abstract

We present a faster distributed broadcasting primitive for the classical radio network model. The most basic distributed radio network broadcasting primitive - called Decay - dates back to a PODC'87 result of Bar-Yehuda, Goldreich, and Itai. In any radio network with some informed source nodes, running Decay for O(d log n + log2 n) rounds informs all nodes at most d hops away from a source with high probability. Since 1987 this primitive has been the most important building block for implementing many other functionalities in radio networks. The only improvements to this decades-old algorithm are slight variations due to [Czumaj, Rytter; FOCS'03] and [Kowalski and Pelc, PODC'03] which achieve the same functionality in O(d log n/d} + log2 n) rounds. To obtain a speedup from this, d and thus also the network diameter need to be near linear, i.e., larger than n1--ε. Our new distributed primitive spreads messages for d hops in O(d log n log log log d + logO(1) n) rounds with high probability. This improves over Decay for any super-polylogarithmic d = logω(1) n and achieves near-optimal O(d log log n) running time for d = nε. This also makes progress on an open question of Peleg.