Miracle-dz/UniFAR-FTUs huggingface dataset:
Improved Approximation Algorithms for Minimizing the Total Weighted Completion Time of Coflows

This paper addresses the challenging scheduling problem of coflows with release times, with the objective of minimizing the total weighted completion time. Previous literature has predominantly concentrated on establishing the scheduling order of coflows. In advancing this research, we contribute by optimizing performance through the determination of the flow scheduling order. The proposed approximation algorithm achieves approximation ratios of $3$ and $2+\frac{1}{LB}$ for arbitrary and zero release times, respectively, where $LB$ is the minimum lower bound of coflow completion time. To further improve time complexity, we streamline linear programming by employing interval-indexed relaxation, thereby reducing the number of variables. As a result, for $\epsilon>0$, the approximation algorithm achieves approximation ratios of $3 + \epsilon$ and $2 + \epsilon$ for arbitrary and zero release times, respectively. Notably, these advancements surpass the previously best-known approximation ratios of 5 and 4 for arbitrary and zero release times, respectively, as established by Shafiee and Ghaderi.
Lesion level–dependent systemic muscle wasting after spinal cord injury is mediated by glucocorticoid signaling in mice

An incomplete mechanistic understanding of skeletal muscle wasting early after spinal cord injury (SCI) precludes targeted molecular interventions. Here, we demonstrated systemic wasting that also affected innervated nonparalyzed (supralesional) muscles and emerged within 1 week after experimental SCI in mice. Systemic muscle wasting caused muscle weakness, affected fast type 2 myofibers preferentially, and became exacerbated after high (T3) compared with low (T9) thoracic paraplegia, indicating lesion level–dependent (“neurogenic”) mechanisms. The wasting of nonparalyzed muscle and its rapid onset and severity beyond what can be explained by disuse implied unknown systemic drivers. Muscle transcriptome and biochemical analysis revealed a glucocorticoid-mediated catabolic signature early after T3 SCI. SCI-induced systemic muscle wasting was mitigated by (i) endogenous glucocorticoid ablation (adrenalectomy) and (ii) pharmacological glucocorticoid receptor (GR) blockade and was (iii) completely prevented after T3 relative to T9 SCI by genetic muscle-specific GR deletion. These results suggest that neurogenic hypercortisolism contributes to a rapid systemic and functionally relevant muscle wasting syndrome early after paraplegic SCI in mice. Lesion level–dependent hypercortisolism induces glucocorticoid-mediated systemic muscle wasting early after paraplegic mouse spinal cord injury. Editor’s summary The loss of muscle mass after spinal cord injury is mainly attributed to disuse. Here, Harrigan and colleagues found that injury at the higher thoracic spinal cord (T3) caused more wasting of paralyzed and nonparalyzed muscles than a more rostral spinal cord injury (T9). Removal of the adrenal glands or glucocorticoid receptor inhibition reduced muscle wasting after T3 injury, and genetic deletion of glucocorticoid receptors from skeletal muscles abolished lesion level–dependent effects on muscle wasting. Although further studies are needed, these results suggest that inhibition of glucocorticoid signaling could help to ameliorate muscle wasting after spinal cord injury. —Daniela Neuhofer
Reshaping Anticoagulation: Factor XI Inhibition in Thrombosis Management

Factor XI is almost dispensable for haemostasis, but its role in thrombosis has become increasingly clear. Targeting factor XI could potentially prevent thrombosis with little or no effect on haemostasis. This review explains the underlying mechanisms of thrombosis and haemostasis and elucidates the rationale for factor XI inhibitors based on the pathophysiology and epidemiological and pre-clinical data. It further outlines the different modes for factor XI inhibition. Finally, the article provides an overview of the current clinical evidence and the ongoing trials for factor XI inhibitors in various clinical indications.
Dengue virus transmission in Italy: surveillance and epidemiological trends up to 2023

Dengue virus circulation is on the rise globally with increased epidemic activity in previously unaffected countries, including within the European region. In 2023, global dengue activity peaked, and Italy reported the highest number of dengue cases and local chains of transmission to date. By curating several sources of information, we introduce a novel data repository focused on dengue reporting in Italy. We integrate geographic, epidemiological, genomic and climatic spatio-temporal data to present an overview of transmission patterns of the past eight years related to circulating viral lineages, geographic distribution, hotspots of reporting, and the theoretical contribution of local climate. This study contributes to a better understanding of the evolving scenario in Italy, with the potential to inform reassessment and planning of adequate national and European public health strategies to manage the emergence of dengue.
Wounded Landscape: Environmental and Social Consequences of (Illegal) Motor Tourism in Forests on the Example of Worek Okrzeszyna (The Central Sudetes on The Polish-Czech Borderland)

Abstract Off-road vehicles (ORVs) have recently become a serious problem not only for natural peripheral areas, but also for those rare green enclaves in heavily urbanised regions. The consequences of motor traffic in naturally valuable areas, including forests, affect the environment together with all its users to different extent. The scale and ubiquity of this type of motor tourism in Poland convinced the authors to research the subject and assess its influence on the forest environment, on the example of the mountains surrounding the region called Worek Okrzeszyna on the Polish-Czech borderland. The authors aimed to determine the scale and character of the phenomenon in forests and environmentally valuable areas in Poland, as well as to assess its scope in the examined research area together with the environmental and social effects. A field inventory of all the trails used by motor tourists was carried out, with particular emphasis on the extent of the network and their environmental consequences. In the ranges surrounding Worek Okrzeszyna from the south, a significant negative impact of illegal motor tourism on the vegetation, soil and relief have been revealed. It occurs wherever the phenomenon takes place: on forest roads, tourist trails and beyond them. Although the main research subject is the pressure of motor tourism on the environment, the authors also raise questions regarding social consequences of the phenomenon (noise, worse aesthetic experience), followed by the limits of tourism as such.
The Silt Dam for Water and Soil Conservation in the Loess Plateau

The building of silt dam is of significance to prevent the Loess Plateau from water and soil loss,to reduce the sediment amount flowed into the Yellow River and realize economic sustainable development in this area.Although the construction of silt dam has gained great achievement,the following questions on the planning and construction of silt dam besides the such questions as slow construction process,under-stantard and shabby conditions of existing facilities should be paid more attention:(1) It should be in accordance with reality in the building area;(2) the integral silt dam system must be constructed according to the geomorphic entitys valley system developed and their evolutionary law;(3) the geomorphic development stage of the situation where the silt dam lies in should not be neglected;and(4)the natural erosion and human-induced accelerating erosion distinguished.
Anomaly detection of cigarette sales using ARIMA on lunar calendar

Anomaly detection of cigarette sales amount and average price of total company, a specific brand and a specific salesman are important for detecting and preventing the illegal circulation of cigarette. By analyzing large amount historical sales records, a cigarette sales foresting model is built to predict the monthly and weekly sales status based on ARIMA model. And then an anomaly detective model is constructed on the predictive result. Although the ARIMA model has been analyzed extensively by researchers and used widely by forecasting practitioners due to its attractive theoretical properties and empirical evidence in its support, there are no empirical investigations have been conducted in the anomaly detection of cigarette sales. Result on the five years sales data from a Chinese city indicate that anomaly detection based on ARIMA on lunar calendar can be an effective way to improve forecasting accuracy and then improved anomaly detection accuracy is achieved.
Homeostatic mitophagy scales mitochondrial networks

Cells scale organelle sizes to ensure physiological function. Here, we uncover a dual role for autophagy in controlling mitochondrial network size with a key function for homeostatic mitophagy. During starvation, non-selective autophagy sustains mitochondrial biogenesis in non-dividing yeast cells resulting in mitochondrial network expansion. Strikingly, Atg32/Bcl2L13-mediated mitophagy scales mitochondria back to pre-starvation size. Without mitophagy, mitochondria size increases two-fold while retaining wildtype-like structural, compositional, and metabolic features. In turn, synthetically elevated mitophagy only mildly reduces mitochondria size, suggesting cells maintain a minimal network size by compensatory biogenesis. Single-cell analysis predicts two metabolically tunable setpoints, mitochondria-to-cell and mitochondria-to-cytosol volume ratios, for mitochondria scaling by autophagy-driven biogenesis and degradation, respectively. Our work reveals how cells use autophagy to scale mitochondria to metabolic and cellular size parameters. One Sentence Summary A homeostatic form of mitophagy controls the network size of mitochondria during starvation.
Persistent enrichment of multidrug resistant Klebsiella in oral and nasal communities during long-term starvation

The human oral and nasal cavities can act as reservoirs for opportunistic pathogens capable of causing acute infection. These microbes asymptomatically colonize the human oral and nasal cavities which facilitates transmission within human populations via the environment, and they routinely possess a clinically-significant antibiotic-resistance genes. Among these opportunistic pathogens, the Klebsiella genus stands out as a notable example, with its members frequently linked to nosocomial infections and multidrug resistance. As with many colonizing opportunistic pathogens, how Klebsiella transitions from an asymptomatic colonizer to a pathogen remains unclear. Here, we explored a possible explanation by investigating the ability of oral and nasal Klebsiella to outcompete their native microbial community members under in vitro starvation conditions, which could be analogous to external hospital environments. When Klebsiella was present within a healthy human oral or nasal sample, the bacterial community composition shifted dramatically under starvation conditions and typically became dominated by Klebsiella. Furthermore, introducing K. pneumoniae exogenously into a native microbial community lacking K. pneumoniae, even at low inoculum, led to repeated dominance under starvation. K.pneumoniae strains isolated from healthy individuals’ oral and nasal cavities also exhibited resistance to multiple classes of antibiotics and were genetically similar to clinical and gut isolates. In addition, we found that in the absence of Klebsiella, other understudied opportunistic pathogens, such as Peptostreptococcus, dominate under starvation conditions. Our findings establish an environmental circumstance that allows for the outgrowth of Klebsiella and other opportunistic pathogens. The ability to outcompete other commensal bacteria and to persist under harsh environmental conditions may contribute to the colonization-to-infection transition of these opportunistic pathogens.
Genome organization in double-stranded DNA viruses observed by cryoET

Double-stranded DNA (dsDNA) viruses package their genetic material into protein cages with diameters usually a few hundred times smaller than the length of their genome. Compressing the relatively stiff and highly negatively charged dsDNA into a small volume is energetically costly and mechanistically enigmatic. Multiple models of dsDNA packaging have been proposed based on various experimental evidence and simulation methods, but direct observation of any viral genome organization is lacking. Here, using cryoET and an improved data processing scheme that utilizes information from the encaging protein shell, we present 3D views of dsDNA genome inside individual viral particles at resolution that densities of neighboring DNA duplexes are readily separable. These cryoET observations reveal a “rod-and-coil” fold of the dsDNA that is conserved among herpes simplex virus type 1 (HSV-1) with a spherical capsid, bacteriophage T4 with a prolate capsid, and bacteriophage T7 with a proteinaceous core inside the capsid. Finally, inspired by the genome arrangement in partially packaged T4 particles, we propose a mechanism for the genome packaging process in dsDNA viruses.
Interleukin-1α links peripheral CaV2.2 channel activation to rapid adaptive increases in heat sensitivity in skin

Neurons have the unique capacity to adapt output in response to changes in their environment. Within seconds, sensory nerve endings can become hypersensitive to stimuli in response to potentially damaging events. The underlying neuroinflammatory response is well studied, but several of the key signaling molecules that mediate sensory hypersensitivity remain unknown. We previously discovered that peripheral voltage-gated CaV2.2 channels in nerve endings in skin are essential for the rapid, transient increase in sensitivity to heat, but not to mechanical stimuli, that accompanies intradermal capsaicin. Here we report that the cytokine interleukin-1α (IL-1α), an alarmin, is necessary and sufficient to trigger rapid heat and mechanical hypersensitivity in skin. Of 20 cytokines screened, only IL-1α was consistently detected in hind paw interstitial fluid in response to intradermal capsaicin and, similar to behavioral sensitivity to heat, IL-1α levels were also dependent on peripheral CaV2.2 channel activity. Neutralizing IL-1α in skin significantly reduced capsaicin-induced changes in hind paw sensitivity to radiant heat and mechanical stimulation. Intradermal IL-1α enhances behavioral responses to stimuli and, in culture, IL-1α enhances the excitability of Trpv1-expressing sensory neurons. Together, our data suggest that IL-1α is the key cytokine that underlies rapid and reversible neuroinflammatory response in skin.
Identification of the Mode of Evolution in Incomplete Carbonate Successions

Background The fossil record provides the unique opportunity to observe evolution over millions of years, but is known to be incomplete. While incompleteness varies spatially and is hard to estimate for empirical sections, computer simulations of geological processes can be used to examine the effects of the incompleteness in silico. We combine simulations of different modes of evolution (stasis, (un)biased random walks) with deposition of carbonate platforms strata to examine how well the mode of evolution can be recovered from fossil time series, and how test results vary between different positions in the carbonate platform and multiple stratigraphic architectures generated by different sea level curves. Results Stratigraphic architecture and position along an onshore-offshore gradient has only a small influence on the mode of evolution recovered by statistical tests. Tests fail to identify the correct mode of evolution in the absence of stratigraphic effects, and support for the correct mode decreases with time series length. Visual examination of trait evolution in lineages shows that rather than stratigraphic incompleteness, maximum hiatus duration determines how much fossil time series differ from the original evolutionary process. Directional evolution is more susceptible to stratigraphic effects, turning it into apparent punctuated equilibrium. In contrast, stasis remains unaffected. Conclusions Tests for the mode of evolution should be reviewed critically, as they do not find good support for the correct (simulated) mode of evolution, even for adequate models that generated the data, in the absence of stratigraphic effects, and for exceptionally long time series. Fossil time series favor the recognition of both stasis and complex, punctuated modes of evolution. Not stratigraphic incompleteness, but the presence of rare, prolonged gaps has the largest effect on trait evolution. This suggests that incomplete sections with regular hiatus frequency and durations can potentially preserve evolutionary history without major biases. Understanding external controls on stratigraphic architectures such as sea level fluctuations is crucial for distinguishing between stratigraphic effects and genuine evolutionary process.
Coevolution of age-structured tolerance and virulence

Hosts can evolve a variety of defences against parasitism, including resistance (which prevents or reduces the spread of infection) and tolerance (which protects against virulence). Some organisms have evolved different levels of tolerance at different life-stages, which is likely to be the result of coevolution with pathogens, and yet it is currently unclear how coevolution drives patterns of age-specific tolerance. Here, we use a model of tolerance-virulence coevolution to investigate how age structure influences coevolutionary dynamics. Specifically, we explore how coevolution unfolds when tolerance and virulence (disease-induced mortality) are age-specific compared to when these traits are uniform across the host lifespan. We find that coevolutionary cycling is relatively common when host tolerance is age-specific, but cycling does not occur when tolerance is the same across all ages. We also find that age-structured tolerance can lead to selection for higher virulence in shorter-lived than in longer-lived hosts, whereas non-age-structured tolerance always leads virulence to increase with host lifespan. Our findings therefore suggest that age structure can have substantial qualitative impacts on host-pathogen coevolution.
Seasonality adaptation patterns of the natural Arabidopsis leaf microbiome over several plant generations are shaped by environmental factors

The leaf-associated microbiome plays a crucial role in plant health and persistence to biotic and abiotic perturbations. However, factors that drive long-term seasonal adaptations of the leaf microbiome, particularly in response to combined stresses, are not well understood. To investigate seasonal adaptation of the leaf microbiome over five years, we analyzed changes in bacterial, fungal and general eukaryotic communities in and on Arabidopsis thaliana leaves from natural populations using molecular markers. We collected samples during spring and fall and used linear regression models and co-occurrence networks to examine the roles of abiotic perturbations, space, and time in shaping the microbiome. Consistent with previous studies, time, space, and host compartment explained more than 18% of microbial community variation. Moreover, we dissect environmental factors that significantly impact microbial community variation. Additionally, we explored the effects of diversity and environmental factors on microbial network complexity and found that decreased diversity was correlated with increased complexity of microbial networks over growing seasons. We were thus able to identify individual microbial taxa that are adapted to specific seasons and their response to abiotic perturbations. We conclude that seasonality adaptation of leaf microbiota is significantly shaped by three environmental factors: radiation, wind speed and drought. Based on our findings we therefore hypothesize that beside space, time and compartment, diversity and stability of microbe-microbe interactions in the phyllosphere are predominantly shaped by a small set of environmental perturbations. Our findings have practical implications for the selection and development of field-adapted probiotics for agricultural applications.
An ancient transcription activator is required for the multiciliogenesis program

Multiciliogenesis is an evolutionarily conserved process required a unique transcriptional program. The mechanisms governing multiciliogenesis are incompletely understood. Here we show that an ancient transcription activator, Edf1, is essential for the multiciliogenesis program. Mice lacking Edf1 exhibit postnatal hydrocephalus and delayed multiciliated cells (MCCs) differentiation. Functional studies reveal that MCCs in Edf1-/- mice have defects in tissue-level polarity and reduced motility. These defects result in abnormal cerebrospinal fluid (CSF) dynamics in vivo, potentially contributing to the development of hydrocephalus. Intriguingly, we found that the expression of pivotal ciliary transcription factors was decreased in Edf1-/- mice. Collectively, our data suggest that Edf1 modulates the multiciliogenesis by regulating the transcription of important ciliary transcription factors required for ciliary gene expression.
ChIP-DIP: A multiplexed method for mapping hundreds of proteins to DNA uncovers diverse regulatory elements controlling gene expression

Gene expression is controlled by the dynamic localization of thousands of distinct regulatory proteins to precise regions of DNA. Understanding this cell-type specific process has been a goal of molecular biology for decades yet remains challenging because most current DNA-protein mapping methods study one protein at a time. To overcome this, we developed ChIP-DIP (ChIP Done In Parallel), a split-pool based method that enables simultaneous, genome-wide mapping of hundreds of diverse regulatory proteins in a single experiment. We demonstrate that ChIP-DIP generates highly accurate maps for all classes of DNA-associated proteins, including histone modifications, chromatin regulators, transcription factors, and RNA Polymerases. Using these data, we explore quantitative combinations of protein localization on genomic DNA to define distinct classes of regulatory elements and their functional activity. Our data demonstrate that ChIP-DIP enables the generation of ‘consortium level’, context-specific protein localization maps within any molecular biology lab.
Resistant gastroenteropancreatic neuroendocrine tumors: a definition and guideline to medical and surgical management

Abstract Gastroenteropancreatic neuroendocrine tumors (NETs), also historically known as carcinoids, are tumors derived of hormone-secreting enteroendocrine cells. Carcinoids may be found in the esophagus, stomach, small intestine, appendix, colon, rectum, or pancreas. The biologic behavior of carcinoids differs based on their location, with gastric and appendiceal NETs among the least aggressive and small intestinal and pancreatic NETs among the most aggressive. Ultimately, however, biologic behavior is most heavily influenced by tumor grade. The incidence of NETs has increased by 6.4 times over the past 40 years. Surgery remains the mainstay for management of most carcinoids. Medical management, however, is a useful adjunct and/or definitive therapy in patients with symptomatic functional carcinoids, in patients with unresectable or incompletely resected carcinoids, in some cases of recurrent carcinoid, and in postoperative patients to prevent recurrence. Functional tumors with persistent symptoms or progressive metastatic carcinoids despite therapy are called “resistant” tumors. In patients with unresectable disease and/or carcinoid syndrome, an array of medical therapies is available, mainly including somatostatin analogues, molecular-targeted therapy, and peptide receptor radionuclide therapy. Active research is ongoing to identify additional targeted therapies for patients with resistant carcinoids.