Miracle-dz/UniFAR-FTUs huggingface dataset:
An integrative, multi-scale, genome-wide model reveals the phenotypic landscape of Escherichia coli

Given the vast behavioral repertoire and biological complexity of even the simplest organisms, accurately predicting phenotypes in novel environments and unveiling their biological organization is a challenging endeavor. Here, we present an integrative modeling methodology that unifies under a common framework the various biological processes and their interactions across multiple layers. We trained this methodology on an extensive normalized compendium for the gram‐negative bacterium Escherichia coli, which incorporates gene expression data for genetic and environmental perturbations, transcriptional regulation, signal transduction, and metabolic pathways, as well as growth measurements. Comparison with measured growth and high‐throughput data demonstrates the enhanced ability of the integrative model to predict phenotypic outcomes in various environmental and genetic conditions, even in cases where their underlying functions are under‐represented in the training set. This work paves the way toward integrative techniques that extract knowledge from a variety of biological data to achieve more than the sum of their parts in the context of prediction, analysis, and redesign of biological systems.
Performance Analysis of SoC Architectures Based on Latency-Rate Servers

This paper presents a method for static performance analysis of SoC architectures. The method is based on a network calculus theory known as LR servers. This network calculus is extended and applied to make it support SoC performance analysis. Performance requirements of subsystems are elegantly captured as traffic flows and associated latency constraints. The SoC infrastructure is modeled as a set of LR servers to validate that the worst-case delays in handling the traffic flows meet the latency constraints. A multi-channel DVB-T set-top box case study demonstrates the power of the method. Key architecture choices, such as schedule or interconnect variant, can be varied easily to support exploration of architecture options.
Nivolumab in Metastatic Non–Small Cell Lung Cancer

Author's disclosures of potential conflicts of interest are found at the end of this article. L ung cancer is the leading cause of cancer deaths in the United States (Ameri-can Cancer Society [ACS], 2015). Non–small cell lung cancer (NSCLC) is one of the most common types of the disease and accounts for 85% to 90% of lung cancer cases (ACS, 2015). Nonsquamous NSCLC accounts for approximately 45% to 60% of all lung cancer cases, whereas squamous NSCLC accounts for approximately 25% to 30% of all lung cancer cases (ACS, 2015). Survival rates vary depending on the stage and type of the cancer and when it is diagnosed. For stage IV NSCLC, the 5-year survival rate is 1% (ACS, 2015). Factors that influence treatments for an individual patient include histology (squamous vs. non-squamous), age, comorbidity, performance status, and preferences and concerns regarding treatment. The presence or absence of driver mutations can be another factor. Patients should have tumor tissue assessed for the presence of a driver mutation, such as mutated epidermal growth factor receptor (EGFR) or the ana-plastic lymphoma kinase (ALK) fusion oncogene (Kerr et al., 2014). Ongoing research into the molecular pathways that drive malignancy in NSCLC has led to the development of agents that target specific molecular pathways in cancer cells (Kerr et al., 2014). Targeted therapies are a significant step forward in treating patients with tumors that contain specific mutations in these pathways. In the United States, several agents have been approved to target these tumors. They include erlotinib, afa-tinib (Gilotrif), and gefitinib (Iressa), which target EGFR signaling; crizo-tinib (Xalkori) and ceritinib (Zykadia), which target ALK rearrangements; bevacizumab (Avastin) and ramuci-rumab (Cyramza), which target vascu-lar endothelial growth factor (VEGF) signaling. Pembrolizumab (Keytruda) and nivolumab (Opdivo) target programmed cell death protein 1 (PD-1) signaling (Lexi-Comp, 2015). Nivolu-mab, one of the agents that target PD-1 signaling, has become of particular interest for its clinical activity against malignant cells. The PD-1 protein is an immune checkpoint receptor expressed by activated T cells (Topalian et al., 2012; Brahmar et al., 2012). In a normal physiologic state, this immune checkpoint exists to protect against inflammation and autoimmunity (Robert et al., 2015). In a neoplastic state, PD-1 binds to its ligands PD-L1 (B7-H1)
Discovering attribute and entity synonyms for knowledge integration and semantic web search

We propose the <i>Context-aware Synonym Suggestion System</i> (<i>CS</i><sup>3</sup>) which learns synonyms from text by using our NLP-based text mining framework, called <i>SemScape</i>, and also from existing evidence in the current knowledge bases (KBs). Using <i>CS</i><sup>3</sup> and our previously proposed knowledge extraction system <i>IBminer</i>, we integrate some of the publicly available knowledge bases into one of the superior quality and coverage, called <i>IKBstore</i>.
Palaeolatitudinal distribution of lithologic indicators of climate in a palaeogeographic framework

Abstract Whether the latitudinal distribution of climate-sensitive lithologies is stable through greenhouse and icehouse regimes remains unclear. Previous studies suggest that the palaeolatitudinal distribution of palaeoclimate indicators, including coals, evaporites, reefs and carbonates, has remained broadly similar since the Permian period, leading to the conclusion that atmospheric and oceanic circulation control their distribution rather than the latitudinal temperature gradient. Here we revisit a global-scale compilation of lithologic indicators of climate, including coals, evaporites and glacial deposits, back to the Devonian period. We test the sensitivity of their latitudinal distributions to the uneven distribution of continental areas through time and to global tectonic models, correct the latitudinal distributions of lithologies for sampling- and continental area-bias, and use statistical methods to fit these distributions with probability density functions and estimate their high-density latitudinal ranges with 50% and 95% confidence intervals. The results suggest that the palaeolatitudinal distributions of lithologies have changed through deep geological time, notably a pronounced poleward shift in the distribution of coals at the beginning of the Permian. The distribution of evaporites indicates a clearly bimodal distribution over the past ~400 Ma, except for Early Devonian, Early Carboniferous, the earliest Permian and Middle and Late Jurassic times. We discuss how the patterns indicated by these lithologies change through time in response to plate motion, orography, evolution and greenhouse/icehouse conditions. This study highlights that combining tectonic reconstructions with a comprehensive lithologic database and novel data analysis approaches provide insights into the nature and causes of shifting climatic zones through deep time.
Research Note - Designing Promotion Ladders to Mitigate Turnover of IT Professionals

Chronic excessive turnover among information technology (IT) professionals has been costly to firms for decades with annual turnover rates as high as 24% even among Computerworld’s “100 Best Places to Work in IT. ” Prior information systems literature has identified two key factors affecting turnover: boundary-spanning roles and low promotability in one’s current firm. We draw on tournament theory, which is primarily concerned with inducing effort in employees, to decompose promotability into two distinct constructs: the likelihood of promotion and benefit from promotion, and demonstrate that each has a distinct role in affecting turnover rates. Our key result is that a job ladder motivating IT professionals with large, infrequent promotions will lead to higher turnover than a job ladder with smaller, more frequent promotions. We describe the conditions under which rearranging the job ladder creates economic value for the firm. We also offer an explanation for the observation that jobs characterized by bou.
Group Communication: Helping or Obscuring Failure Diagnosis? (CMU-PDL-06-107)

Replicated client-server systems are often based on underlying group communication protocols that provide totally ordered, reliable delivery of messages. However, in the face of a performance fault (e.g, memory leak, packet loss) at a single node, group communication protocols can cause correlated performance degradations at non-faulty nodes. We explore the impact of performance-degradation faults on token-ring and quorum-based group communication protocols in replicated systems. By empirically evaluating these protocols, in the presence of a variety of injected faults, we investigate which metrics are the most/least appropriate for failure diagnosis. We show that group communication protocols can both help and obscure root-cause analysis, and present an approach for fingerpointing the faulty node by monitoring OS-level and protocol-level metrics. Our empirical evaluation suggests that the root-cause of the failure is either the node exhibiting the most anomalies in a given window of time or the node with an “odd-man-out” behavior, e.g., if a node displays a surge in context-switch rate while the other nodes display a dip in the same metric.
The Oxidative Stress Response Highly Depends on Glucose and Iron Availability in Aspergillus fumigatus

Pathogens have to cope with oxidative, iron- and carbon(glucose)-limitation stresses in the human body. To understand how combined iron–carbon limitation alters oxidative stress responses, Aspergillus fumigatus was cultured in glucose–peptone or peptone containing media supplemented or not with deferiprone as an iron chelator. Changes in the transcriptome in these cultures were recorded after H2O2 treatment. Responses to oxidative stress were highly dependent on the availability of glucose and iron. Out of the 16 stress responsive antioxidative enzyme genes, only the cat2 catalase–peroxidase gene was upregulated in more than two culturing conditions. The transcriptional responses observed in iron metabolism also varied substantially in these cultures. Only extracellular siderophore production appeared important regardless of culturing conditions in oxidative stress protection, while the enhanced synthesis of Fe-S cluster proteins seemed to be crucial for oxidative stress treated iron-limited and fast growing (glucose rich) cultures. Although pathogens and host cells live together in the same place, their culturing conditions (e.g., iron availability or occurrence of oxidative stress) can be different. Therefore, inhibition of a universally important biochemical process, like Fe-S cluster assembly, may selectively inhibit the pathogen growth in vivo and represent a potential target for antifungal therapy.
Creating a Coreference Resolution System for Polish

Although the availability of the natural language processing tools and the development of metrics to evaluate them increases, there is a certain gap to fill in that field for the less-resourced languages, such as Polish. Therefore the projects which are designed to extend the existing tools for diverse languages are the best starting point for making these languages more and more covered. This paper presents the results of the first attempt of the co\-re\-fe\-rence resolution for Polish using statistical methods. It presents the conclusions from the process of adapting the Beautiful Anaphora Resolution Toolkit (BART; a system primarily designed for the English language) for Polish and collates its evaluation results with those of the previously implemented rule-based system. Finally, we describe our plans for the future usage of the tool and highlight the upcoming research to be conducted, such as the experiments of a larger scale and the comparison with other machine learning tools.
Perceived Risk of Ischemic and Bleeding Events in Acute Coronary Syndromes

Background— Acute coronary syndrome registries report the use of incomplete guideline therapies, especially among the highest risk patients. Whether this treatment gap results from misperceptions of risk by physicians is uncertain. Methods and Results— The Perceived Risk of Ischemic and Bleeding Events in Acute Coronary Syndrome Patients (PREDICT) study was a prospective acute coronary syndrome registry in Australia, China, India, and Russia, involving 58 hospitals between May 2009 and February 2011. In-hospital care and events up to 6 months were assessed. At least 2 clinicians involved in patient care estimated the untreated risk and change in risk with each therapy. Physician risk assessment and objective risk measures (eg, Global Registry of Acute Coronary Events [GRACE] score) for death, death/myocardial infarction, and bleeding events were compared using the c statistic and integrated discrimination improvement. In total, 1542 patients and 4230 patient-specific physician estimates were obtained. Of responding clinicians, 81.9% were cardiovascular specialists (years of practice: mean [SD], 11.5 [7.7] years). The median physician-perceived risk of 6-month death was 25% (interquartile range, 14%–35%). The GRACE score was superior to physician estimation (c statistic: GRACE score, 0.812 [95% confidence interval, 0.772–0.851] versus physician, 0.652 [95% confidence interval, 0.596–0.708]; P<0.0001). The GRACE score added to clinician intuition improved discrimination (integrated discrimination improvement, 0.0632 [SE, 0.012]; P<0.0001). Invasive management correlated with physician-estimated risk but not with GRACE risk. Among patients not at high risk by physician estimation, increased risk by GRACE score was associated with higher mortality (3.7% versus 0.8%; P<0.001). Conclusions— Objective risk assessment provides superior risk discrimination when compared with physician-estimated risk. Whether systematic use of objective risk stratification improves clinical outcomes should be studied in appropriately designed clinical trials.
Real-time Robust Manhattan Frame Estimation: Global Optimality and Applications

Most man-made environments, such as urban and indoor scenes, consist of a set of parallel and orthogonal planar structures. These structures are approximated by Manhattan world assumption and be referred to Manhattan Frame (MF). Given a set of inputs such as surface normals or vanishing points, we pose an MF estimation problem as a consensus set maximization that maximizes the number of inliers over the rotation search space. Conventionally this problem can be solved by a branch-and-bound framework which mathematically guarantees global optimality. However, the computational time of the conventional branch-and-bound algorithms is rather far from real-time performance. In this paper, we propose a novel bound computation method on an efficient measurement domain for MF estimation, i.e., the extended Gaussian image (EGI). By relaxing the original problem, we can compute the bounds in real-time performance, while preserving global optimality. Furthermore, we quantitatively and qualitatively demonstrate the performance of the proposed method for various synthetic and real-world data. We also show the versatility of our approach through three different applications: extension to multiple MF estimation, video stabilization and line clustering.
Stress response of boreal woodland caribou, moose, and wolves to disturbance in eastern Manitoba

Disturbance by anthropogenic activities may cause chronic (long-term) stress in wildlife and contribute to population declines. Declines of boreal woodland caribou (Rangifer tarandus caribou; hereinafter referred as caribou) across Canada have been attributed to anthropogenic disturbance, but the physiological stress response of caribou to disturbance has not been examined. To understand the stress response of caribou to disturbance, we measured cortisol concentrations in guard hair collected from 89 female caribou between 2009 and 2011 in eastern Manitoba. We compared cortisol concentrations among five caribou populations occupying areas with varying levels of disturbance, and examined annual variation in cortisol concentrations among the three most southern populations. We also estimated home range sizes of 55 GPScollared caribou and examined how home range size varied with cortisol concentrations. Within each home range, we quantified disturbance characteristics (roads, transmission lines, cottages, and logged and burned areas) and landscape features (lakes, black spruce, and jack pine habitat), and used model selection to determine the combination of disturbance features that best explained variation in caribou cortisol concentrations. Cortisol concentrations were greatest for the three most southern caribou populations and were higher in 2009 compared to 2011 for these populations. Furthermore, cortisol concentrations increased with decreasing home range size, and proportion of intermediate logging (6 – 21 years) best explained variation in cortisol concentrations. These results suggest that caribou respond negatively to intermediate logging, and constraints on home range size can elevate cortisol concentrations. Since increased cortisol concentrations can affect survival and reproduction, continued monitoring of caribou cortisol
An Exploratory Study on the Spatial Relationship Between Regional Cortical Volume Changes and White Matter Integrity in Multiple Sclerosis

Multiple sclerosis (MS) is a chronic inflammatory central nervous system disorder with a neurodegenerative component. While in the past, MS has been predominantly viewed as a white matter (WM) disease, gray matter (GM) pathology receives increasing attention in MS research. In this study, we tested hypothesis-free for a possible spatial relationship between cortical volume changes and disturbed integrity of projecting WM tracts. We used voxel-based morphometry (VBM), lesion probability maps (LPM), and probabilistic tractography to compare brain magnetic resonance imaging (MRI) scans obtained at 3 Tesla of 15 low disabled MS patients with 15 matched healthy controls (HCs). Areas of decreased cortical volume in the patients identified by VBM were used as seeds for tractography. Volume in two cortical areas in the left inferior frontal gyrus (IFG) and the left lateral occipital cortex (LOC) was reduced in patients compared to HCs. Starting from the IFG-region, tractography suggested impaired connections between left and right portions of the frontal lobe in the patients. Using the LOC as a seed, in patients, the left inferior longitudinal and fronto-occipital pathways appeared disintegrated compared to HCs. Swapping the seeds to homologous contralateral areas showed similar results for frontal, but different results for occipital brain areas. This at least partly could be explained by differential interference with WM lesions. These findings suggest a regional dependence between cortical GM and WM tract alterations in MS patients. While confirmation in larger and more heterogenic samples is needed, this study indicates that combining several MRI methods (VBM, LPM, and Probabilistic Tractography) may provide important insights into interacting processes related to the fiber tract and GM changes in MS.
Voter Apathy in Nigerian Electoral Democracy: An Insidious Enigma to National Development

This paper examines voter apathy in Nigerian electoral democracy as an insidious enigma to national development, with an emphasis on the 2023 General Elections. Elections in democracies play a vital role in ensuring the representation of popular will and securing the legitimacy of the political system. However, in situations where voter apathy is pronounced in the electoral processes of democratic countries, national development in such countries is nearly defeated. Voter apathy remains an insidious enigma for national development, and Nigeria provides an example of such a country. What is the way out? To answer this question, the paper made use of the decision-making theory by Richard Synder as its theoretical framework, adopted a qualitative research design, relied on secondary sources of data, and analyzed the collected data using the qualitative content data analysis method. The findings of the study revealed the factors causing voters’ apathy in Nigerian electoral democracy and their consequences on the country’s national development. Recommendations were made based on the findings.
Characterization of chromatin domains by 3D fluorescence microscopy: An automated methodology for quantitative analysis and nuclei screening

Fluorescence microscopy has provided a route to qualitatively analyze features of nuclear structures and chromatin domains with increasing resolution. However, it is becoming increasingly important to develop tools for quantitative analysis. Here, we present an automated method to quantitatively determine the enrichment of several endogenous factors, immunostained in pericentric heterochromatin domains in mouse cells. We show that this method permits an unbiased characterization of changes in the enrichment of several factors with statistical significance from a large number of nuclei. Furthermore, the nuclei can be sorted according to the enrichment value of these factors. This method should prove useful to monitor events related to changes in the amount, rather than the presence or absence, of any factor. By adapting a few parameters, it could be extended to other nuclear structures and the benefit of using available software will permit its use in many biological labs.
PTCH1 Gene Variants, mRNA Expression, and Bioinformatics Insights in Mexican Cutaneous Squamous Cell Carcinoma Patients

Simple Summary Skin cancer represents a prevalent and significant global health concern. Our study focused on comprehending cutaneous squamous cell carcinoma in the Mexican population through the examination of genetic variants of the PTCH1 gene, the assessment of its mRNA’s relative expression, and the utilization of bioinformatics tools. Despite the absence of statistically significant associations in the experimental results, integrating bioinformatics was imperative to understand the impact of the analyzed variants on protein function, splicing, expression, and disease-related aspects. This contributes to our overarching comprehension of non-melanoma skin cancer development. Further investigation is crucial to gain a comprehensive understanding of the in vivo role of these genetic variants. Abstract Background: Skin cancer is one of the most frequent types of cancer, and cutaneous squamous cell carcinoma (cSCC) constitutes 20% of non-melanoma skin cancer (NMSC) cases. PTCH1, a tumor suppressor gene involved in the Sonic hedgehog signaling pathway, plays a crucial role in neoplastic processes. Methods: An analytical cross-sectional study, encompassing 211 cSCC patients and 290 individuals in a control group (CG), was performed. A subgroup of samples was considered for the relative expression analysis, and the results were obtained using quantitative real-time PCR (qPCR) with TaqMan® probes. The functional, splicing, and disease-causing effects of the proposed variants were explored via bioinformatics. Results: cSCC was predominant in men, especially in sun-exposed areas such as the head and neck. No statistically significant differences were found regarding the rs357564, rs2236405, rs2297086, and rs41313327 variants of PTCH1, or in the risk of cSCC, nor in the mRNA expression between the cSCC group and CG. A functional effect of rs357564 and a disease-causing relation to rs41313327 was identified. Conclusion: The proposed variants were not associated with cSCC risk in this Mexican population, but we recognize the need for analyzing larger population groups to elucidate the disease-causing role of rare variants.