Miracle-dz/UniFAR-FTUs huggingface dataset:
A biased random key genetic algorithm applied to the VRPTW with skill requirements and synchronization constraints

We applied a Biased Random Key Genetic Algorithm (BRKGA) to solve the Vehicle Routing Problem with Time Windows and Synchronization Constraints. Additionally, both vehicles and clients are skilled, and each client can require up to two distinct skills to be serviced. On double-skilled clients, the operations of each skill should be performed by different vehicles, either simultaneously or respecting a precedence order. Those requirements introduce nonlinearities on the problem, in the sense that a small change on a single route potentially impacts all the other routes of the solution, making it hard to define an effective local search procedure. To circumvent this difficulty, we approached the problem using a genetic algorithm that evolves the sequence in which the services are inserted into the routes. We assessed the performance of our solution method using instances from the literature of the home health care problem. The genetic algorithm outperformed the previous best-known solutions found by a fix-and-optimize matheuristic by up to 25%, using less than half of computational times reported previously. The BRKGA demonstrated to be able to perform well both in exploration and exploitation in the solution space of the problem.
Black Walnut: A Nut Crop for the Midwestern United States

Eastern black walnut (Juglansnigra L.), is a native tree species valued both for its timber and nuts. Individual trees require excellent soils with adequate moisture for maximum wood and nut productivity. The vast majority of black walnut nutmeat production is centered in the western part of the species' native range and is predominantly derived from wild, unimproved sources. Historically, the size of this crop has ranged from 4.5 to 15.9 million kilograms (fresh weight, without hull) with less than 1% obtained from improved cultivars. Alternate bearing is common in this species, primarily as a result of susceptibility to walnut anthracnose Gnomonia leptostyla (Fr.) Ces. & De Not. Significant reductions in nut productivity caused by walnut curculio (Conotrachelus retentus Say) are common for unimproved, wild trees. Based on a collection of 65 nut cultivars established by the University of Missouri, black walnut exhibits significant genetic variation for a range of commercially important nut traits, including precocity, percent kernel, nut bearing habit, anthracnose tolerance, season length, and yield efficiency. Exploiting this variation through traditional plant breeding techniques will result in new, improved varieties in the future. Defining improved cultural practices that will significantly impact yield and nut quality remains an area of active investigation. Such knowledge will need to be combined with improved cultivars that are well adapted to local growing conditions to ensure the commercial success of this species over the long run.
Transmission Quality Optimization in Inter-Datacenter WAN

Inter-datacenter wide area network provides high bandwidth and low delay connections for data center nodes in different regions. However, different cross data center traffic has different requirements for the network. It is very important for network operators to understand the requirements of upper applications and improve the network quality of services. Some existing traffic engineering schemes are devoted to improving the utilization of network bandwidth. However, they fail to consider the impact on transmission quality caused by failure to complete within the deadline when making scheduling schemes. In this paper, we aim to improve the overall transmission quality of the network, i.e. make full use of network bandwidth resources to improve the acceptance ratio and completion ratio of large transfer tasks without affecting the completion time of interactive flow. In order to achieve the above goals, we formulate the problem of transmission quality optimization and transforms the piecewise and discontinuous optimization objectives of the original problem into a form that is easy to solve. In addition, we propose a progressive approximation algorithm (PAA) to find an approximate solution for the problem in a feasible time range. Finally, based on the real Inter-datacenter WAN topology and different traffic patterns, a large-scale simulation experiment is carried out, which proves that the algorithm proposed in this paper can effectively improve the transmission quality of large transfer in Inter-Datacenter WAN.
Transgenerational fitness effects of lifespan extension by dietary restriction in Caenorhabditis elegans

Dietary restriction increases lifespan in a broad variety of organisms and improves health in humans. However, long-term transgenerational consequences of dietary interventions are poorly understood. Here we investigated the effect of dietary restriction by temporary fasting (TF) on mortality risk, age-specific reproduction and fitness across three generations of descendants in C. elegans. We show that while TF robustly reduces mortality risk and improves late-life reproduction in the parental generation (P0), it has a wide range of both positive and deleterious effects on future generations (F1-F3). Remarkably, great-grandparental exposure to TF in early-life reduces fitness and increases mortality risk of F3 descendants to such an extent that TF no longer promotes a lifespan extension. These findings reveal that transgenerational trade-offs accompany the instant benefits of dietary restriction underscoring the need to consider fitness of future generations in pursuit of healthy ageing.
A predictive model of gene expression reveals the role of regulatory motifs in the mating response of yeast

Cells use signaling pathways to receive and process information about their environment. These systems are nonlinear, relying on feedback and feedforward regulation to respond appropriately to changing environmental conditions. Mathematical models developed to describe signaling pathways often fail to show predictive power, because the models are not trained on data that probe the diverse time scales on which feedforward and feedback regulation operate. We addressed this limitation using microfluidics to expose cells to a broad range of dynamic environmental conditions. In particular, we focus on the well-characterized mating response pathway of S. cerevisiae (yeast). This pathway is activated by mating pheromone and initiates the transcriptional changes required for mating. Although much is known about the molecular components of the mating response pathway, less is known about how these components function as a dynamical system. Our experimental data revealed that pheromone-induced transcription persists following removal of pheromone and that long-term adaptation of the transcriptional response occurs when pheromone exposure is sustained. We developed a model of the regulatory network that captured both persistence and long-term adaptation of the mating response. We fit this model to experimental data using an evolutionary algorithm and used the parameterized model to predict scenarios for which it was not trained, including different temporal stimulus profiles and genetic perturbations to pathway components. Our model allowed us to establish the role of four regulatory motifs in coordinating pathway response to persistent and dynamic stimulation.
The GET pathway safeguards against non-imported mitochondrial protein stress

Deficiencies in mitochondrial import cause the toxic accumulation of non-imported mitochondrial precursor proteins. Numerous fates for non-imported mitochondrial precursors have been identified, including proteasomal destruction, deposition into protein aggregates, and mis-targeting to other organelles. Amongst organelles, the endoplasmic reticulum (ER) has emerged as a key destination for non-imported mitochondrial proteins, but how ER-targeting of these proteins is achieved remains unclear. Here, we show that the guided entry of tail-anchored proteins (GET) complex is required for ER-targeting of endogenous mitochondrial multi-transmembrane proteins. Without a functional GET pathway, non-imported mitochondrial proteins destined for the ER are alternatively sequestered into Hsp42-dependent protein foci. The ER targeting of non-imported mitochondrial proteins by the GET complex prevents cellular toxicity and facilitates re-import of mitochondrial proteins from the ER via the recently identified ER-SURF pathway. Overall, this study outlines an important and unconventional role for the GET complex in mitigating stress associated with non-imported mitochondrial proteins.
Follicle Stem Cells (FSCs) in the Drosophila ovary; a critique of published studies defining the number, location and behavior of FSCs

A paper by Reilein et al., (2017) presented several key new insights into the behavior of adult Follicle Stem Cells (FSCs) in the Drosophila ovary, including overwhelming evidence that each ovariole hosts a large number of FSCs (about 14-16) maintained by population asymmetry (Reilein et al., 2017), rather than just two FSCs, dividing with largely individually asymmetric outcomes, as originally proposed (Margolis and Spradling, 1995; Nystul and Spradling, 2007). Here we provide further discussion asserting the merits of the conclusions of Reilein et al., (2017) and the deficiencies in the contrary assertions recently presented by Fadiga and Nystul (Fadiga and Nystul, 2019). The principles that we discuss here, particularly with regard to lineage tracing and population asymmetry, are common to the investigation of most types of adult stem cell and should therefore be instructive and of interest to investigators studying any type of adult stem cell. The improved understanding of FSC numbers, location and behavior afforded by Reilein et al., (2017) and Reilein et al., (2018) can only provide a firm foundation for future progress once they are widely appreciated and seen to be resistant to challenge, as described in detail here.
Structure and allosteric regulation of human IDH3 holoenzyme

Human NAD-dependent isocitrate dehydrogenase or IDH3 catalyzes the decarboxylation of isocitrate into α-ketoglutarate in the TCA cycle. We here report the structure of the IDH3 holoenzyme, in which the αβ and αγ heterodimers assemble the α2βγ heterotetramer via their clasp domains, and two α2βγ heterotetramers assemble the (α2βγ)2 heterooctamer via the β and γ subunits. The functional roles of the key residues involved in the assembly and allosteric regulation are validated by mutagenesis and kinetic studies. The allosteric site plays an important role but the pseudo allosteric site plays no role in the allosteric activation; the activation signal from the allosteric site is transmitted to the active sites of both heterodimers via the clasp domains; and the N-terminus of the γ subunit plays a critical role in the formation and function of the holoenzyme. These findings reveal the molecular mechanism of the assembly and allosteric regulation of human IDH3 holoenzyme.
Man overboard event detection from RGB and thermal imagery: possibilities and limitations

A man overboard is an emergency incident, in which fast detection is the most crucial factor, for the quickest and most efficient recovery of the victim. As such, efficient monitoring methodologies should be employed. A variety of sensors is available today, supporting a continuous monitoring process, regardless of environmental conditions; RGB and thermal are two commonly used sensors. At the same time, several algorithms and techniques have been tested and proved to be efficient in human detection and situation recognition tasks. However, to this day a coherent methodology for fall detection over multiple sensors on a large-scale deployment, complying with related ISO standards on extremely low false positive alerts, has not been implemented. In this paper, we investigate the possibilities as well as the limitations of man overboard vision-based systems' development based on RGB and thermal imagery.
Socio-Spatial Relationships in Dairy Cows

Farm animals may serve as models for evaluating social networks in a controlled environment. We used an automated system to track, at fine temporal and spatial resolution (once per minute, +/- 50 cm) every individual in six herds of dairy cows (Bos taurus). We then analysed the data using social network analyses. Relationships were based on non-random attachment and avoidance relationships in respect to synchronous use and distances observed in three different functional areas (activity, feeding and lying). We found that neither synchrony nor distance between cows was strongly predictable among the three functional areas. The emerging social networks were tightly knit for attachment relationships and less dense for avoidance relationships. These networks loosened up from the feeding and lying area to the activity area, and were less dense for relationships based on synchronicity than on median distance with respect to node degree, relative size of the largest cluster, density and diameter of the network. In addition, synchronicity was higher in dyads of dairy cows that had grown up together and shared their last dry period. This last effect disappeared with increasing herd size. Dairy herds can be characterized by one strongly clustered network including most of the herd members with many non-random attachment and avoidance relationships. Closely synchronous dyads were composed of cows with more intense previous contact. The automatic tracking of a large number of individuals proved promising in acquiring the data necessary for tackling social network analyses.
A Whole-Cortex Probabilistic Diffusion Tractography Connectome

Abstract The WU-Minn Human Connectome Project (HCP) is a publicly-available dataset containing state-of-the-art structural magnetic resonance imaging (MRI), functional MRI (fMRI), and diffusion MRI (dMRI) for over a thousand healthy subjects. While the planned scope of the HCP included an anatomic connectome, resting-state fMRI (rs-fMRI) forms the bulk of the HCP’s current connectomic output. We address this by presenting a full-cortex connectome derived from probabilistic diffusion tractography and organized into the HCP-MMP1.0 atlas. Probabilistic methods and large sample sizes are preferable for whole-connectome mapping as they increase the fidelity of traced low-probability connections. We find that overall, connection strengths are lognormally distributed and decay exponentially with tract length, that connectivity reasonably matches macaque histologic tracing in homologous areas, that contralateral homologs and left-lateralized language areas are hyperconnected, and that hierarchical similarity influences connectivity. We compare the dMRI connectome to existing rs-fMRI and cortico-cortico-evoked potential connectivity matrices and find that it is more similar to the latter. This work helps fulfill the promise of the HCP and will make possible comparisons between the underlying structural connectome and functional connectomes of various modalities, brain states, and clinical conditions.
Noise-induced scaling in skull suture interdigitation

Sutures, the thin, soft tissue between skull bones, serve as the major craniofacial growth centers during postnatal development. In a newborn skull, the sutures are straight; however, as the skull develops, the sutures wind dynamically to form an interdigitation pattern. Moreover, the final winding pattern had been shown to have fractal characteristics. Although various molecules involved in suture development have been identified, the mechanism underlying the pattern formation remains unknown. In a previous study, we reproduced the formation of the interdigitation pattern in a mathematical model combining an interface equation and a convolution kernel. However, the generated pattern had a specific characteristic length, and the model was unable to produce a fractal structure with the model. In the present study, we focused on the anterior part of the sagittal suture and formulated a new mathematical model with time–space-dependent noise that was able to generate the fractal structure. We reduced our previous model to represent the linear dynamics of the centerline of the suture tissue and included a time–space-dependent noise term. We showed theoretically that the final pattern from the model follows a scaling law due to the scaling of the dispersion relation in the full model, which we confirmed numerically. Furthermore, we observed experimentally that stochastic fluctuation of the osteogenic signal exists in the developing skull, and found that actual suture patterns followed a scaling law similar to that of the theoretical prediction. Author summary Skull sutures (thin, undifferentiated tissue between bones) act as the growth centers for the skull. Sutures are straight at birth but later develop an interdigitated pattern that ultimately becomes a fractal structure. While our previous mathematical model of sutures generated a periodic pattern, the mechanism underlying the fractal structure formation remained to be elucidated. Here, we focused only on the anterior part of the sagittal suture and formulated a reduced model representing the initial linear phase of pattern formation with the addition of a time–space-dependent noise term. We showed analytically that the model generates patterns with a scaling law. This result was confirmed numerically and experimentally.
Inferring cellular trajectories from scRNA-seq using Pseudocell Tracer

Single cell RNA sequencing (scRNA-seq) can be used to infer a temporal ordering of dynamic cellular states. Current methods for the inference of cellular trajectories rely on unbiased dimensionality reduction techniques. However, such biologically agnostic ordering can prove difficult for modeling complex developmental or differentiation processes. The cellular heterogeneity of dynamic biological compartments can result in sparse sampling of key intermediate cell states. This scenario is especially pronounced in dynamic immune responses of innate and adaptive immune cells. To overcome these limitations, we develop a supervised machine learning framework, called Pseudocell Tracer, which infers trajectories in pseudospace rather than in pseudotime. The method uses a supervised encoder, trained with adjacent biological information, to project scRNA-seq data into a low-dimensional cellular state space. Then a generative adversarial network (GAN) is used to simulate pesudocells at regular intervals along a virtual cell-state axis. We demonstrate the utility of Pseudocell Tracer by modeling B cells undergoing immunoglobulin class switch recombination (CSR) during a prototypic antigen-induced antibody response. Our results reveal an ordering of key transcription factors regulating CSR, including the concomitant induction of Nfkb1 and Stat6 prior to the upregulation of Bach2 expression. Furthermore, the expression dynamics of genes encoding cytokine receptors point to the existence of a regulatory mechanism that reinforces IL-4 signaling to direct CSR to the IgG1 isotype.
Defining the signalling determinants of a posterior ventral spinal cord identity in human neuromesodermal progenitor derivatives

ABSTRACT The anteroposterior axial identity of motor neurons (MNs) determines their functionality and vulnerability to neurodegeneration. Thus, it is a crucial parameter in the design of strategies aiming to produce MNs from human pluripotent stem cells (hPSCs) for regenerative medicine/disease modelling applications. However, the in vitro generation of posterior MNs corresponding to the thoracic/lumbosacral spinal cord has been challenging. Although the induction of cells resembling neuromesodermal progenitors (NMPs), the bona fide precursors of the spinal cord, offers a promising solution, the progressive specification of posterior MNs from these cells is not well defined. Here, we determine the signals guiding the transition of human NMP-like cells toward thoracic ventral spinal cord neurectoderm. We show that combined WNT-FGF activities drive a posterior dorsal pre-/early neural state, whereas suppression of TGFβ-BMP signalling pathways promotes a ventral identity and neural commitment. Based on these results, we define an optimised protocol for the generation of thoracic MNs that can efficiently integrate within the neural tube of chick embryos. We expect that our findings will facilitate the comparison of hPSC-derived spinal cord cells of distinct axial identities. Summary: An efficient strategy is described for the in vitro generation of previously hard-to-produce posterior spinal cord progenitors and MNs exhibiting a thoracic axial and, in particular, preganglionic columnar identity.
Human brain function during pattern separation follows hippocampal and neocortical connectivity gradients

Episodic memory is our ability to remember past events accurately. Pattern separation, the process of of orthogonalizing similar aspects of external information into nonoverlapping representations, is one of its mechanisms. Converging evidence suggests a pivotal role of the hippocampus, in concert with neocortical areas, in this process. The current study aimed to identify principal dimensions of functional activation associated with pattern separation in hippocampal and neocortical areas, in both healthy individuals and patients with lesions to the hippocampus. Administering a pattern separation fMRI paradigm to a group of healthy adults, we detected task-related activation in bilateral hippocampal and distributed neocortical areas. Capitalizing on manifold learning techniques applied to parallel resting-state fMRI data, we could identify that hippocampal and neocortical activity patterns were efficiently captured by their principal gradients of intrinsic functional connectivity, which follows the hippocampal long axis and sensory-fugal cortical organization. Functional activation patterns and their alignment with these principal dimensions were altered in patients. Notably, inter-individual differences in the concordance between task-related activity and intrinsic functional gradients were correlated with pattern separation performance in both patients and controls. Our work outlines a parsimonious approach to capture the functional underpinnings of episodic memory processes at the systems level, and to decode functional reorganization in clinical populations.
BurstZ: a bandwidth-efficient scientific computing accelerator platform for large-scale data

We present BurstZ, a bandwidth-efficient accelerator platform for scientific computing. While accelerators such as GPUs and FPGAs provide enormous computing capabilities, their effectiveness quickly deteriorates once the working set becomes larger than the on-board memory capacity, causing the performance to become bottlenecked either by the communication bandwidth between the host and the accelerator. Compression has not been very useful in solving this issue due to the difficulty of efficiently compressing floating point numbers, which scientific data often consists of. Most compression algorithms are either ineffective with floating point numbers, or has a high performance overhead. BurstZ is an FPGA-based accelerator platform which addresses the bandwidth issue via a novel hardware-optimized floating point compression algorithm, which we call sZFP. We demonstrate that BurstZ can completely remove the communication bottleneck for accelerators, using a 3D stencil-code accelerator implemented on a prototype BurstZ implementation. Evaluated against hand-optimized implementations of stencil code accelerators of the same architecture, our BurstZ prototype outperformed an accelerator without compression by almost 4X, and even an accelerator with enough memory for the entire dataset by over 2X. BurstZ improved communication efficiency so much, our prototype was even able to outperform the upper limit projected performance of an optimized stencil core with ideal memory access characteristics, by over 2X.