Miracle-dz/UniFAR-FTUs huggingface dataset:
Recombination and mutational robustness in neutral fitness landscapes

Mutational robustness quantifies the effect of random mutations on fitness. When mutational robustness is high, most mutations do not change fitness or have only a minor effect on it. From the point of view of fitness landscapes, robust genotypes form neutral networks of almost equal fitness. Using deterministic population models it has been shown that selection favors genotypes inside such networks, which results in increased mutational robustness. Here we demonstrate that this effect is massively enhanced by recombination. Our results are based on a detailed analysis of mesa-shaped fitness landscapes, where we derive precise expressions for the dependence of the robustness on the landscape parameters for recombining and non-recombining populations. In addition, we carry out numerical simulations on different types of random holey landscapes as well as on an empirical fitness landscape. We show that the mutational robustness of a genotype generally correlates with its recombination weight, a new measure that quantifies the likelihood for the genotype to arise from recombination. We argue that the favorable effect of recombination on mutational robustness is a highly universal feature that may have played an important role in the emergence and maintenance of mechanisms of genetic exchange. Author summary Two long-standing and seemingly unrelated puzzles in evolutionary biology concern the ubiquity of sexual reproduction and the robustness of organisms against genetic perturbations. Using a theoretical approach based on the concept of a fitness landscape, in this article we argue that the two phenomena may in fact be closely related. In our setting the hereditary information of an organism is encoded in its genotype, which determines it to be either viable or non-viable, and robustness is defined as the fraction of mutations that maintain viability. Previous work has demonstrated that the purging of non-viable genotypes from the population by natural selection leads to a moderate increase in robustness. Here we show that genetic recombination acting in combination with selection massively enhances this effect, an observation that is largely independent of how genotypes are connected by mutations. This suggests that the increase of robustness may be a major driver underlying the evolution of sexual recombination and other forms of genetic exchange throughout the living world.
Jamming-Assisted Eavesdropping Over Parallel Fading Channels

Unlike passive eavesdropping, proactive eavesdropping is recently proposed to use jamming to moderate a suspicious link’s communication rate for facilitating simultaneous eavesdropping. This paper advances the proactive eavesdropping research by considering a practical half-duplex mode for the legitimate monitor (e.g., a government agency) and dealing with the challenging case that the suspicious link opportunistically communicates over parallel fading channels. To increase eavesdropping success probability, we propose cognitive jamming for the monitor to change the suspicious link’s long-term belief on the parallel channels’ distributions and thereby induce it to transmit more likely over a smaller subset of unjammed channels with a lower transmission rate. As the half-duplex monitor cannot eavesdrop the channel that it is simultaneously jamming to, our jamming design should also control the probability of such “own goal” that occurs when the suspicious link chooses one of the jammed (uneavesdroppable) channels to transmit. We formulate the optimal jamming design problem as a mixed integer nonlinear programming (MINLP) and show that it is non-convex. Nevertheless, we prove that the monitor should optimally use the maximum jamming power if it decides to jam, for maximally reducing the suspicious link’s communication rate and driving the suspicious link out of the jammed channels. Then we manage to simplify the MINLP to integer programming and reveal a fundamental trade-off in deciding the number of jammed channels: jamming more channels helps reduce the suspicious link’s communication rate for overhearing more clearly but increases own goal probability and thus decreases eavesdropping success probability. Finally, we extend our study to the two-way suspicious communication scenario and show that there is another interesting trade-off in deciding the common jammed channels for balancing bidirectional eavesdropping performances. Numerical results show that our optimized jamming-assisted eavesdropping schemes greatly increase eavesdropping success probability as compared with the conventional passive eavesdropping.
Association between Peripheral Blood Inflammatory Markers, Endothelial Dysfunction Markers, and Depression

The authors present an analysis of current research and their own data on the link between endothelial dysfunction (ED) and the severity of depression in middle-aged patients with cerebral microangiopathy. Levels of peripheral inflammatory and endothelial dysfunction markers were measured using the enzyme-linked immunosorbent assay (ELISA). The results of the comparative and correlation analyses showed a statistically significant correlation between the severity of depression and increased levels of inflammatory, as well as endothelial dysfunction
A tanglegram Kuratowski theorem

A tanglegram consists of two rooted binary plane trees with the same number of leaves and a perfect matching between the two leaf sets. Tanglegrams are drawn with the leaves on two parallel lines, the trees on either side of the strip created by these lines, and the perfect matching inside the strip. If this can be done without any edges crossing, a tanglegram is called planar. We show that every nonplanar tanglegram contains one of two nonplanar 4‐leaf tanglegrams as an induced subtanglegram, which parallels Kuratowski's Theorem.
Peripheral vision: a new killer app for smart glasses

Most smart glasses have a small and limited field of view. The head-mounted display often spreads between the human central and peripheral vision. In this paper, we exploit this characteristic to display information in the peripheral vision of the user. We introduce a mobile peripheral vision model, which can be used on any smart glasses with a head-mounted display without any additional hardware requirement. This model taps into the blocked peripheral vision of a user and simplifies multi-tasking when using smart glasses. To display the potential applications of this model, we implement an application for indoor and outdoor navigation. We conduct an experiment on 20 people on both smartphone and smart glass to evaluate our model on indoor and outdoor conditions. Users report to have spent at least 50% less time looking at the screen by exploiting their peripheral vision with smart glass. 90% of the users Agree that using the model for navigation is more practical than standard navigation applications.
Functional Coupling of Cav2.3 and BK Potassium Channels Regulates Action Potential Repolarization and Short-Term Plasticity in the Mouse Hippocampus

Voltage-gated ion channels are essential for signal generation and propagation in neurons and other excitable cells. The high-voltage activated calcium-channel Cav2.3 is expressed throughout the central and peripheral nervous system, and within CA1 hippocampal pyramidal neurons it is localized throughout the somato-dendritic region and dendritic spines. Cav2.3 has been shown to provide calcium for other calcium-dependent potassium channels including small-conductance calcium-activated potassium channels (SK), but big-conductance calcium-activated potassium channels (BK) have been thought to be activated by calcium from all known voltage-gated calcium channels, except Cav2.3. Here we show for the first time that CA1 pyramidal cells which lack Cav2.3 show altered action potential (AP) waveforms, which can be traced back to reduced SK- and BK-channel function. This change in AP waveform leads to strengthened synaptic transmission between CA1 and the subiculum, resulting in increased short-term plasticity. Our results demonstrate that Cav2.3 impacts cellular excitability through functional interaction with BK channels, impacting communication between hippocampal subregions.
Computational Hardness of Certifying Bounds on Constrained PCA Problems

Given a random $n \times n$ symmetric matrix $\boldsymbol W$ drawn from the Gaussian orthogonal ensemble (GOE), we consider the problem of certifying an upper bound on the maximum value of the quadratic form $\boldsymbol x^\top \boldsymbol W \boldsymbol x$ over all vectors $\boldsymbol x$ in a constraint set $\mathcal{S} \subset \mathbb{R}^n$. For a certain class of normalized constraint sets $\mathcal{S}$ we show that, conditional on certain complexity-theoretic assumptions, there is no polynomial-time algorithm certifying a better upper bound than the largest eigenvalue of $\boldsymbol W$. A notable special case included in our results is the hypercube $\mathcal{S} = \{ \pm 1 / \sqrt{n}\}^n$, which corresponds to the problem of certifying bounds on the Hamiltonian of the Sherrington-Kirkpatrick spin glass model from statistical physics. Our proof proceeds in two steps. First, we give a reduction from the detection problem in the negatively-spiked Wishart model to the above certification problem. We then give evidence that this Wishart detection problem is computationally hard below the classical spectral threshold, by showing that no low-degree polynomial can (in expectation) distinguish the spiked and unspiked models. This method for identifying computational thresholds was proposed in a sequence of recent works on the sum-of-squares hierarchy, and is believed to be correct for a large class of problems. Our proof can be seen as constructing a distribution over symmetric matrices that appears computationally indistinguishable from the GOE, yet is supported on matrices whose maximum quadratic form over $\boldsymbol x \in \mathcal{S}$ is much larger than that of a GOE matrix.
Reimplantable Microdrive for Long-Term Chronic Extracellular Recordings in Freely Moving Rats

Extracellular recordings of electrical activity in freely moving rats are fundamental to understand brain function in health and disease. Such recordings require a small-size, lightweight device that includes movable electrodes (microdrive) to record either a new set of neurons every day or the same set of neurons over time. Ideally, microdrives should be easy to implant, allowing precise and smooth displacement of electrodes. The main caveat of most commercially available microdrives is their relatively short half-life span, in average ranging from weeks to a month. For most experiments, recording days–weeks is sufficient, but when the experiment depends on training animals for several months, it is crucial to develop new approaches. Here, we present a low-cost, reusable, and reimplantable device design as a solution to extend chronic recordings to long-term. This device is composed of a baseplate that is permanently fixed to the rodent’s skull, as well as a reusable and replaceable microdrive that can be attached and detached from the baseplate, allowing its implantation and reimplantation. Reimplanting this microdrive is particularly convenient when no clear neuronal signal is present, or when the signal gradually decays across days. Our microdrive incorporates a mechanism for moving a 16 tungsten-wire bundle within a small (∼15 mm3) lightweight device (∼4 g). We present details of the design, manufacturing, and assembly processes. As a proof of concept, we show that recordings of the nucleus accumbens core (NAcc) in a freely behaving rat are stable over a month. Additionally, during a lever-press task, we found, as expected, that NAc single-unit activity was associated with rewarded lever presses. Furthermore, we also show that NAc shell (NAcSh) responses evoked by freely licking for sucrose, consistent with our previously published results, were conserved from a first implant to a second microdrive reimplant in the same rat, notably showing reimplantation is possible without overtly affecting the functional responses of the area of interest. In sum, here we present a novel microdrive design (low-cost, small size, and light weight) that can be used for long-term chronic recordings and reimplanted in freely behaving rats.
Cellular characteristics of skeletal muscle in selected strains of pigs and mice and the unselected controls.

: Skeletal muscle growth of swine differing in rate of growth and muscularity was studied by analysis of DNA, RNA, and protein in the semitendinosus muscle of fast growing domestic lean pigs (Yorkshire) and the slow-growing feral obese pigs (Ossabaw). Both lean and obese strains were fed ad libitum corn and soybean mean diet containing 14% protein. The pigs were slaughtered at 6 months of age. The Yorkshire pig had significantly greater body and muscle weights (P less than 0.005) Total DNA, RNA, and protein in semitendinosus muscles were significantly greater in the Yorkshire pigs (P less than 0.005). RNA/DNA and protein/DNA ratios were significantly different between the Yorkshire and Ossabaw pigs. These data suggest that the greater muscle growth in the Yorkshire pigs is achieved by greater cell numbers and size. The response of skeletal muscle cells and fiber characteristics to selection was studied in two strains of mice by analysis of DNA, RNA, and histological measurement of muscle fibers. Both strains were fed ad libitum on laboratory rat chow diet. They were sacrificed at 12 months of age. Leg muscle DNA and RNA were significantly greater in the mice selected for rapid growth rate as compared to the control (P less than 0.005 and P less than .10, respectively). Measurements of the semimembranosus muscle reveal that the growth strain had significantly greater muscle weight (P less than .01) and muscle length (P less than 0.005). Histological measurements of the same muscle showed that the growth strain had significantly greater fiber number (P less than 0.005) and larger fiber size (P less than 0.005) than the controls. It would appear that the greater muscle cellularity (DNA) in growth strain mice is accompanied by greater muscle length, fiber number, and fiber diameter.
Role of pancreatoscopy in management of pancreatic disease: A systematic review

BACKGROUND Per-oral pancreatoscopy (POP) plays a role in the diagnosis and therapy of pancreatic diseases. With recent technological advances, there has been renewed interest in this modality. AIM To evaluate the efficacy and safety of POP in management of pancreatic stone disease and pancreatic ductal neoplasia. METHODS To determine the safety and efficacy of POP in the management of pancreatic diseases, a systematic search was conducted in MEDLINE, EMBASE and Ovid. Articles in languages other than English and case reports were excluded. All published case series were eligible. Data specific to POP were extracted from studies, which combined cholangiopancreatoscopy. Ten studies were included in the analysis of POP therapy for pancreatic stone disease, and 15 case series satisfied the criteria for inclusion for the role of POP in the management of pancreatic ductal neoplasia. The examined data were subcategorized according to adjunctive modalities, such as direct tissue sampling, cytology, the role of intraoperative POP, intraductal ultrasound (IDUS) and POP combined with image-enhancing technology. RESULTS The success rate for complete ductal stone clearance ranged from 37.5%-100%. Factors associated with failure included the presence of strictures, multiple stones and the inability to visualize the target area. Although direct visualization can identify malignant and premalignant conditions, there is significant overlap with benign diseases. Visually-directed biopsies provide a high degree of accuracy, and represent a unique approach for tissue acquisition in patients with ductal abnormalities. Addition of pancreatic fluid cytology increases diagnostic yield for indeterminate lesions. Protrusions larger than 3 mm noted on IDUS are significantly more likely to be associated with malignancy. The rate of adverse events associated with POP ranged from 0%-35%. CONCLUSION Current evidence supports wider adoption of pancreatoscopy, as it is safe and effective. Improved patient selection and utilization of novel technologies may further enhance its role in managing pancreatic disease.
The decycling number and maximum genus of cubic graphs

Let ∇(G) and γM(G) denote the minimum size of a decycling set and maximum genus of a graph G, respectively. For a connected cubic graph G of order n, it is shown that ∇(G)+γM(G)=n2+1 . Applying the formula, we obtain some new results on the decycling number and maximum genus of cubic graphs. Furthermore, it is shown that the number of vertices of a decycling set S in a k‐regular graph G is |S|=1k−1{β(G)+c+mS′−1} , where c and mS′ are the number of components of G−S and the number of edges in G[S] , respectively. Therefore, S is minimum if and only if c+mS′−1 is minimum. As an application, this leads to a lower bound ∇(G)≥⌈β(G)k−1⌉ for ∇(G) of a k‐regular graph G. In many cases this bound may be sharp.
Under the Hood of Membership Inference Attacks on Aggregate Location Time-Series

Aggregate location statistics are used in a number of mobility analytics to express how many people are in a certain location at a given time (but not who). However, prior work has shown that an adversary with some prior knowledge of a victim's mobility patterns can mount membership inference attacks to determine whether or not that user contributed to the aggregates. In this paper, we set to understand why such inferences are successful and what can be done to mitigate them. We conduct an in-depth feature analysis, finding that the volume of data contributed and the regularity and particularity of mobility patterns play a crucial role in the attack. We then use these insights to adapt defenses proposed in the location privacy literature to the aggregate setting, and evaluate their privacy-utility trade-offs for common mobility analytics. We show that, while there is no silver bullet that enables arbitrary analysis, there are defenses that provide reasonable utility for particular tasks while reducing the extent of the inference.
A Novel Test of Pure Irrelevance-Induced Blindness

Load theory claims that bottom-up attention is possible under conditions of low perceptual load but not high perceptual load. At variance with this claim, a recent one-trial study showed that under low load, with only two colors in the display – a ring and a disk –, an instruction to process only one of the two stimuli led to better memory performance for the color of the relevant than of the irrelevant stimulus. Control experiments showed that if instructed to pay attention to both objects, participants were able to memorize both colors. Thus, stimulus irrelevance diminished the likelihood of memory for a color stimulus under low perceptual-load conditions. Yet, we noted less than optimal design features in that prior study: a lack of more implicit priming measures of memory or attention and an interval between color stimulus presentation and memory test that probably exceeded 500 ms. We took care of these problems in the current one-trial study by improving the retrieval displays while leaving the encoding displays as in the original study and found that the results only partly replicated prior findings. In particular, there was no evidence of irrelevance-induced blindness under conditions in which a ring was designated as relevant, surrounding an irrelevant disk. However, a continuously cumulative meta-analysis across past and present experiments showed that our results do not refute the irrelevance-induced effects entirely. We conclude with recommendations for future tests of load theory.
Machine learning-assisted directed protein evolution with combinatorial libraries

Significance Proteins often function poorly when used outside their natural contexts; directed evolution can be used to engineer them to be more efficient in new roles. We propose that the expense of experimentally testing a large number of protein variants can be decreased and the outcome can be improved by incorporating machine learning with directed evolution. Simulations on an empirical fitness landscape demonstrate that the expected performance improvement is greater with this approach. Machine learning-assisted directed evolution from a single parent produced enzyme variants that selectively synthesize the enantiomeric products of a new-to-nature chemical transformation. By exploring multiple mutations simultaneously, machine learning efficiently navigates large regions of sequence space to identify improved proteins and also produces diverse solutions to engineering problems. To reduce experimental effort associated with directed protein evolution and to explore the sequence space encoded by mutating multiple positions simultaneously, we incorporate machine learning into the directed evolution workflow. Combinatorial sequence space can be quite expensive to sample experimentally, but machine-learning models trained on tested variants provide a fast method for testing sequence space computationally. We validated this approach on a large published empirical fitness landscape for human GB1 binding protein, demonstrating that machine learning-guided directed evolution finds variants with higher fitness than those found by other directed evolution approaches. We then provide an example application in evolving an enzyme to produce each of the two possible product enantiomers (i.e., stereodivergence) of a new-to-nature carbene Si–H insertion reaction. The approach predicted libraries enriched in functional enzymes and fixed seven mutations in two rounds of evolution to identify variants for selective catalysis with 93% and 79% ee (enantiomeric excess). By greatly increasing throughput with in silico modeling, machine learning enhances the quality and diversity of sequence solutions for a protein engineering problem.
Sauvé-Kapandji Procedure with Limited Wrist Fusion for Disorders of the Distal Radioulnar Joint in Patients with Rheumatoid Arthritis

Background: The wrist is affected in as many as 95% of patients who have rheumatoid arthritis (RA). Involvement of the distal radioulnar joint leads to dorsal dislocation of the ulnar head that can cause pain, weakness, decreased forearm rotation, and rupture of the extensor tendons. When there is arthritis of the radiocarpal joint the problem become worthy. Aim: to assess the results of Sauvé-Kapandji procedure with limited wrist fusion in improving the wrist function in patients with RA. Patients and Methods: This operation was performed in seventeen wrists in seventeen consecutive patients with RA in whom Sauvé-Kapandji procedure was done in the inferior radioulnar joint with limited radiolunate fusion. Results: fifteen patients had no pain in the region of the distal radioulnar joint. Osseous union was achieved in all cases. The average time to osseous union was 8.7 weeks. The visual analog scores decreased from a mean of 7.2 before the operation to 2.0 after the operation (p < 0.01). Conclusion: Sauvé-Kapandji procedure with limited wrist fusion significantly improves the wrist functions in patients with RA.