Computer Sciences Commons^™

A Review Of Threat Vectors To Dna Sequencing Pipelines, Tyler Rector

Cybersecurity Undergraduate Research Showcase

Bioinformatics is a steadily growing field that focuses on the intersection of biology with computer science. Tools and techniques developed within this field are quickly becoming fixtures in genomics, forensics, epidemiology, and bioengineering. The development and analysis of DNA sequencing and synthesis have enabled this significant rise in demand for bioinformatic tools. Notwithstanding, these bioinformatic tools have developed in a research context free of significant cybersecurity threats. With the significant growth of the field and the commercialization of genetic information, this is no longer the case. This paper examines the bioinformatic landscape through reviewing the biological and cybersecurity threats within …

Deficiency Of Acute-Phase Serum Amyloid A Exacerbates Sepsis-Induced Mortality And Lung Injury In Mice, Ailing Ji, Andrea C. Trumbauer, Victoria P. Noffsinger, Luke W. Meredith, Brittany Dong, Qian Wang, Ling Guo, Xiangan Li, Frederick C. De Beer, Nancy R. Webb, Lisa R. Tannock, Marlene E. Starr, Christopher M. Waters, Preetha Shridas

Saha Cardiovascular Research Center Faculty Publications

Serum amyloid A (SAA) is a family of proteins, the plasma levels of which may increase >1000-fold in acute inflammatory states. We investigated the role of SAA in sepsis using mice deficient in all three acute-phase SAA isoforms (SAA-TKO). SAA deficiency significantly increased mortality rates in the three experimental sepsis mouse models: cecal ligation and puncture (CLP), cecal slurry (CS) injection, and lipopolysaccharide (LPS) treatments. SAA-TKO mice had exacerbated lung pathology compared to wild-type (WT) mice after CLP. A bulk RNA sequencing performed on lung tissues excised 24 h after CLP indicated significant enrichment in the expression of genes associated …

Software Jimenae Allows Efficient Dynamic Simulations Of Boolean Networks, Centrality And System State Analysis, Martin Kaltdorf, Tim Breitenbach, Stefan Karl, Maximilian Fuchs, David Komla Kessie, Eric Psota, Martina Prelog, Edita Sarukhanyan, Regina Ebert, Franz Jakob, Gudrun Dandekar, Muhammad Naseem, Chunguang Liang, Thomas Dandekar

All Works

The signal modelling framework JimenaE simulates dynamically Boolean networks. In contrast to SQUAD, there is systematic and not just heuristic calculation of all system states. These specific features are not present in CellNetAnalyzer and BoolNet. JimenaE is an expert extension of Jimena, with new optimized code, network conversion into different formats, rapid convergence both for system state calculation as well as for all three network centralities. It allows higher accuracy in determining network states and allows to dissect networks and identification of network control type and amount for each protein with high accuracy. Biological examples demonstrate this: (i) High plasticity …

Emerging Sensing, Imaging, And Computational Technologies To Scale Nano-To Macroscale Rhizosphere Dynamics – Review And Research Perspectives, Amir H. Ahkami, Odeta Qafoku, Tiina Roose, Quanbing Mou, Yi Lu, Zoe G. Cardon, Yuxin Wu, Chunwei Chou, Joshua B. Fisher, Tamas Varga, Pubudu Handakumbura, Jayde A. Aufrecht, Arunima Bhattacharjee, James J. Moran

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The soil region influenced by plant roots, i.e., the rhizosphere, is one of the most complex biological habitats on Earth and significantly impacts global carbon flow and transformation. Understanding the structure and function of the rhizosphere is critically important for maintaining sustainable plant ecosystem services, designing engineered ecosystems for long-term soil carbon storage, and mitigating the effects of climate change. However, studying the biological and ecological processes and interactions in the rhizosphere requires advanced integrated technologies capable of decoding such a complex system at different scales. Here, we review how emerging approaches in sensing, imaging, and computational modeling …

Regulation Of Regeneration In Arabidopsis Thaliana, Md Khairul Islam, Sai Teja Mummadi, Sanzhen Liu, Hairong Wei

Michigan Tech Publications

We employed several algorithms with high efficacy to analyze the public transcriptomic data, aiming to identify key transcription factors (TFs) that regulate regeneration in Arabidopsis thaliana. Initially, we utilized CollaborativeNet, also known as TF-Cluster, to construct a collaborative network of all TFs, which was subsequently decomposed into many subnetworks using the Triple-Link and Compound Spring Embedder (CoSE) algorithms. Functional analysis of these subnetworks led to the identification of nine subnetworks closely associated with regeneration. We further applied principal component analysis and gene ontology (GO) enrichment analysis to reduce the subnetworks from nine to three, namely subnetworks 1, 12, and 17. …

An Overview Of Elements And Relations: Aspects Of A Scientific Metaphysics, Martin Zwick

Complex Systems Faculty Publications and Presentations

A talk on my book, Elements and Relations: Aspects of a Scientific Metaphysics. Book description:

This book develops the core proposition that systems theory is an attempt to construct an “exact and scientific metaphysics,” a system of general ideas central to science that can be expressed mathematically. Collectively, these ideas would constitute a non-reductionist “theory of everything” unlike what is being sought in physics. Inherently transdisciplinary, systems theory offers ideas and methods that are relevant to all of the sciences and also to professional fields such as systems engineering, public policy, business, and social work. To demonstrate the generality …

Green Synthesized Silver Nanoparticles-Based Sensing For Monitoring Water Pollution: An Updated Review, Muhamad Allan Serunting, Muhammad Ali Zulfikar, Henry Setiyanto, Dian Ayu Setyorini, Vienna Saraswaty

Karbala International Journal of Modern Science

Water is a basic human need and has been heavily contaminated. Therefore, it becomes a concern to remove the pollutant and monitor its quality. The removal methods include precipitation, filtration, adsorption, and photodegradation. Meanwhile, the monitoring can be done by measuring and analyzing the contaminant using spectrophotometry and chromatography. Nevertheless, those methods usually need a complicated preparation, and are expensive. Thus, a simple method is necessary to overcome these drawbacks by developing a sensor. In recent years, the sensor performance has been enhanced by using nanomaterials, such as silver nanoparticles (AgNPs). AgNPs can be synthesized using plant extracts through a …

Synthesis And Characterization Of Zirconium Oxide Nanoparticles Using Z. Officinale And S. Aromaticum Plant Extracts For Antibacterial Application, M. J. Tuama, M. F. A. Alias

Karbala International Journal of Modern Science

Abstract The dramatic rise in bacterial infections and increased resistance to conventional antibiotics has led to the exploration of biologically derived nanomaterials to counteract bacterial activity. Nanotechnology, which deals with materials at the atomic or molecular level, is a promising way to achieve this goal. Zirconium oxide nanoparticles (ZrO2NPs) have shown strong antibacterial effects due to the increased surface-to-volume ratio at the nanoscale. This study focused on the production of ZrO2NPs in an environmentally friendly manner, which included extracts from Zingiber officinale (ginger), where G-ZrO2NPs were produced, and Syzygium aromaticum (clove), which produced S-ZrO2NPs. Various techniques were used, such as …

Motif-Cluster: A Spatial Clustering Package For Repetitive Motif Binding Patterns, Mengyuan Zhou

School of Computing: Dissertations, Theses, and Student Research

Previous efforts in using genome-wide analysis of transcription factor binding sites (TFBSs) have overlooked the importance of ranking potential significant regulatory regions, especially those with repetitive binding within a local region. Identifying these homogenous binding sites is critical because they have the potential to amplify the binding affinity and regulation activity of transcription factors, impacting gene expression and cellular functions. To address this issue, we developed an open-source tool Motif-Cluster that prioritizes and visualizes transcription factor regulatory regions by incorporating the idea of local motif clusters. Motif-Cluster can rank the significant transcription factor regulatory regions without the need for experimental …

Depaul Digest

DePaul Magazine

College of Education Professor Jason Goulah fosters hope, happiness and global citizenship through DePaul’s Institute for Daisaku Ikeda Studies in Education. Associate Journalism Professor Jill Hopke shares how to talk about climate change. News briefs from DePaul’s 10 colleges and schools: Occupational Therapy Standardized Patient Program, Financial Planning Certificate program, Business Education in Technology and Analytics Hub, Racial Justice Initiative, Teacher Quality Partnership grant, Intimate Partner Violence and Brain Injury collaboration, School of Music Career Closet, Sports Photojournalism course, DePaul Migration Collaborative’s Solutions Lab, Inclusive Screenwriting courses. New appointments: School of Music Dean John Milbauer, College of Education Dean Jennifer …

Modification Of Chitosan Using Glycidyl Methacrylate-Grafted Cellulose (Gmagcell/ Chi) For Methylene Blue Adsorption, Haya Fathana, Rahmi Rahmi, Muhammad Adlim, Surya Lubis

Karbala International Journal of Modern Science

In this study, a glycidyl methacrylate-grafted cellulose/chitosan (GMA-g-Cell/Chi) film was successfully prepared and characterized. GMA-g-Cell was obtained from the grafting process of cellulose derived from sugarcane bagasse using glycidyl methacrylate (GMA). The cellulose grafting process was obtained using 20% GMA for 4 hours at 60oC. The percentage of grafting (PG) and grafting efficiency (GE) values for these parameters were 516 and 60.28%, respectively. Chitosan was modified with GMA-g-Cell and has higher adsorption capacity and tensile strength than chitosan. The adsorption kinetics tend to follow the pseudo-first-order adsorption kinetics model, with Qe and k1 being 7 mg/g and 0.067 g/mg. minute. …

Statistical And Machine Learning Approaches To Describe Factors Affecting Preweaning Mortality Of Piglets, Md Towfiqur Rahman, Tami M. Brown-Brandl, Gary A. Rohrer, Sudhendu R. Sharma, Vamsi Manthena, Yeyin Shi

Department of Agricultural and Biological Systems Engineering: Faculty Publications

High preweaning mortality (PWM) rates for piglets are a significant concern for the worldwide pork industries, causing economic loss and well-being issues. This study focused on identifying the factors affecting PWM, overlays, and predicting PWM using historical production data with statistical and machine learning models. Data were collected from 1,982 litters from the United States Meat Animal Research Center, Nebraska, over the years 2016 to 2021. Sows were housed in a farrowing building with three rooms, each with 20 farrowing crates, and taken care of by well-trained animal caretakers. A generalized linear model was used to analyze the various sow, …

Fortifying Iot Against Crimpling Cyber-Attacks: A Systematic Review, Usman Tariq, Irfan Ahmed, Muhammad Attique Khan, Ali Kashif Bashir

Karbala International Journal of Modern Science

The rapid growth and increasing demand for Internet of Things (IoT) devices in our everyday lives create exciting opportunities for human involvement, data integration, and seamless automation. This fully interconnected ecosystem considerably impacts crucial aspects of our lives, such as transportation, healthcare, energy management, and urban infrastructure. However, alongside the immense benefits, the widespread adoption of IoT also brings a complex web of security threats that can influence society, policy, and infrastructure conditions. IoT devices are particularly vulnerable to security violations, and industrial routines face potentially damaging vulnerabilities. To ensure a trustworthy and robust security framework, it is crucial to …

New Quantum Genetic Algorithm Based On Constrained Quantum Optimization, Mohammed R. Almasaoodi, Abdulbasit M. A. Sabaawi, Sara El Gaily, Sándor Imre

Karbala International Journal of Modern Science

In the past decades, many quantum algorithms have been developed. The main obstacle that prevents the widespread implementation of these algorithms is the small size of the available quantum computer in terms of qubits. Blind Quantum Computation (BQC) holds the promise of handling this issue by delegating computation to quantum remote devices. Here, we introduce a novel Constrained Quantum Genetic Algorithm (CQGA) that selects the optimum extreme (minimum or maximum) value of a constrained goal function (or a vast unsorted database) with very low computational complexity. Since the convergence speed to the optimal solution for the Constrained Classical Genetic Algorithm …

Deep Learning For Plant Bioinformatics: An Explainable Gradient-Based Approach For Disease Detection, Muhammad Shoaib, Babar Shah, Nasir Sayed, Farman Ali, Rafi Ullah, Irfan Hussain

All Works

Emerging in the realm of bioinformatics, plant bioinformatics integrates computational and statistical methods to study plant genomes, transcriptomes, and proteomes. With the introduction of high-throughput sequencing technologies and other omics data, the demand for automated methods to analyze and interpret these data has increased. We propose a novel explainable gradient-based approach EG-CNN model for both omics data and hyperspectral images to predict the type of attack on plants in this study. We gathered gene expression, metabolite, and hyperspectral image data from plants afflicted with four prevalent diseases: powdery mildew, rust, leaf spot, and blight. Our proposed EG-CNN model employs a …

Recent Advances In Crispr/Cas9-Assisted Gene Therapy, Apeksha Srivastava, Shikha Chauhan, Vishal Ahuja

Karbala International Journal of Modern Science

CRISPR/Cas9 (Clustered regularly interspaced short palindromic repeats) is an exponentially growing tool with wide-spread applications in therapeutics like gene modifications that focus on altering the hereditary material to repair or eliminate any defective gene-causing diseases like cancer, AIDS (Acquired immunodeficiency syndrome), etc. It also includes the identification of the target sequence with the help of sgRNA followed by the substitution of a malfunction-ing gene with a normal version. It offers high efficiency, specificity, and post-gene-editing efficacy, but have also some off-target impressions, and immunogenic effects. The contribution of CRISPR/Cas9 has already been proved primarily in in-vitro studies using animal germ …

Optical, Structural, And Electrochemical Properties Of P3ht:Y6 Photoactive Layer For Organic Photovoltaics, Hassan Tarikhum B., Furqan Almyahi, Basil Ali

Karbala International Journal of Modern Science

Recently, organic photovoltaics (OPV) have emerged as a promising technology for environmentally friendly energy production. Achieving high performance in OPV requires the discovery of novel compounds. This article aims to study the optical, structural, electrochemical, and electrical properties of a P3HT:Y6 blend. The UV-visible spectra of the blend provided insight into how composition affects the optoelectronic properties of OPV devices. The optimised P3HT:Y6 ratio (0.6:1) resulted in the largest redshift and the highest absorption intensity. Raman and X-ray diffraction tests showed low aggregation and low crystallinity of the polymer P3HT as Y6 content increased. In the OPV devices, the best …

Estimation Of Water Quality Of Dikhu River Of Nagaland Through A Combination Of Water Quality Index And Principal Component Analysis Techniques., Lanuyanger Longchar, Wati Temjen, Khikeya Semy, Wati Lemla

Karbala International Journal of Modern Science

Monitoring the physico-chemical attributes of water is essential for determining water quality. The present study explores the effect of various anthropogenic factors on the quality of Dikhu River, Nagaland. Water samples from three sampling stations were compared against three standards: Indian Council of Medical Research, Bureau of Indian Standards, and World Health Organization. Although all parameters were within the permissible limits, the Water Quality Index categorized all sites during the rainy season as "poor quality", highlighting anthropogenic impacts. A principal component analysis created a Minimum Data Set (MDS) explaining 100%, 93.27%, and 96.26% of the total variance for the three …

Gaxin2-Xo3 Surface Pyramids Interaction With Formaldehyde: Thermodynamic And Sensing Analysis, Mudar Ahmed Abdulsattar

Karbala International Journal of Modern Science

GaxIn2-xO3 surface pyramids' electronic structures are investigated using density functional theory, including dispersion corrections. Application of GaxIn2-xO3 surface pyramids as a gas sensor for formaldehyde is also performed and compared with experimental findings. These findings show that the energy gap of these pyramids follows closely with the bulk values. The energy gap increases between the two limits, In2O3 and Ga2O3. Applying GaxIn2-xO3 surface pyramids as a gas sensor uses transition state theory formalism. Thermodynamic quantities such as activation Gibbs energy, enthalpy, and entropy are needed for temperature-dependent calculations. A comparison of sensor response which is proportional to reaction rate as …

Intelligence Versus Inferno: How Artificial Intelligence Can Be Used To Monitor And Manage Wildfires In Europe, Maxwell Feldman

Independent Study Project (ISP) Collection

Escalating wildfire occurrences in Europe, particularly in the southern Mediterranean region, are presenting significant challenges to socioeconomic, environmental, and ecosystem services. The increasing frequency and severity of these wildfires are straining resources and emphasizing the need for a better understanding of the relationship between suppression capacity and fire behavior in wildfire management. The following research addresses the urgent need for more proactive, knowledge-based, and technologically driven fire management strategies, throughout all four stages of wildfire response – fuel and land management, fire preparedness, fire suppression, and post-fire management. Artificial Intelligence (AI) is becoming increasingly significant in climate change adaptation, especially …

Tracing And Segmentation Of Molecular Patterns In 3-Dimensional Cryo-Et/Em Density Maps Through Algorithmic Image Processing And Deep Learning-Based Techniques, Salim Sazzed

Computer Science Theses & Dissertations

Understanding the structures of biological macromolecules is highly important as they are closely associated with cellular functionalities. Comprehending the precise organization of actin filaments is crucial because they form the dynamic cytoskeleton, which offers structural support to cells and connects the cell’s interior with its surroundings. However, determining the precise organization of actin filaments is challenging due to the poor quality of cryo-electron tomography (cryo-ET) images, which suffer from low signal-to-noise (SNR) ratios and the presence of missing wedge, as well as diverse shape characteristics of actin filaments. To address these formidable challenges, the primary component of this dissertation focuses …

Evaluating A Large Language Model’S Ability To Solve Programming Exercises From An Introductory Bioinformatics Course, Stephen R. Piccolo, Paul Denny, Andrew Luxton-Reilly, Samuel H. Payne, Perry G. Ridge

Faculty Publications

Life scientists frequently write computer code when doing research. Computer programming can aid researchers in performing tasks that are not supported by existing tools. Programming can also help researchers to implement analytical logic in a way that documents their steps and thus enables others to repeat those steps. Many educational resources are available to teach computer programming, but this skill remains challenging for many researchers and students to master. Artificial-intelligence tools like OpenAI’s ChatGPT are able to interpret human-language requests to generate code. Accordingly, we evaluated the extent to which this technology might be used to perform programming tasks described …

Eggshell-Alginate Composites (Eacs) As Eco-Friendly Adsorbents For Rhodamine B Uptake From Aqueous Solutions, Rusnadi Rusnadi, Mar’Atus Sholihah, Nurrahmi Handayani, Muhammad Ali Zulfikar

Karbala International Journal of Modern Science

The contamination of wastewater by Rhodamine B (RhB) poses a significant environmental concern due to its negative impacts on aesthetics, ecosystems, and human well-being. This study successfully synthesized eco-friendly egg-shell-alginate composites (EACs) as adsorbents by combining alginate solution, eggshell powder, and a 2% CaCl2 solu-tion. Characterization techniques including FTIR, SEM, TGA, and SAA were employed to analyze the EACs. FTIR analysis revealed characteristic absorption peaks corresponding to -OH groups, C=O groups, C-O groups, and the pres-ence of CO32-. The structural analysis confirmed the physical mixture of functional groups from eggshells and alginate, resulting in a homogeneous EACs mixture. TGA analysis …

Synthesizing Of Alginate Coated-Silver Nanoparticles Core-Shell For Detecting Of S-Naproxen Enantiomer In Pharmaceutical Formulation, Abdolrasol Barazandeh, Ghasem Najafpour-Darz, Afshar Alihossein, Sohrab Kazemi

Karbala International Journal of Modern Science

Core-shell nanoparticles were used in a unique direct UV-Vis spectrophotometric technique to detect the S-naproxen enantiomer. Silver nanoparticles (Ag NPs) covered with sodium alginate (Alg) shell, a naturally occurring biopolymer, made the core of the nanostructure. To name a few, TEM, FESEM, UV-Visible, DLS, ZP, AFM, XRD, EDX and FT-IR are among the analytical methods used to analyze the creation of the core-shell structure. Based on obtained results, spherical Ag@ Alg NPs with an average size of 27.4 nm (DTEM), hydrolytic size of 46 nm (DDLS) and surface charge of -60.9 mV were successfully synthesized. The effect of various reaction …

Multiple Structural And Functional Annotations Based In-Silico Characterization Of Q9brx8 Protein, Eiman Zahid, Muhammad Farhan Sarwar

Karbala International Journal of Modern Science

Numerous proteins found in humans are poorly understood because there is a dearth of experimental evidence. Hypothetical proteins (HPs) or uncharacterized proteins are the terms used to describe these proteins. In this work, one of these proteins, Q9BRX8, is investigated using in-silico or bioinformatics tools to reveal its significant properties. In this regard, NCBI for the sequence retrieval, ProtParam tool for analysis of physiochemical properties, SOPMA for secondary structure prediction, SWISS-Model for homology modelling, STRING for protein-protein interaction and HDOCK for protein-protein docking analysis among other tools, were incorporated. The physiochemical characteristics indicated that Q9BRX8, which has an instability score …

In Vitro Antioxidant, Anti-Inflammatory, And Photoprotective Activities Of Aqueous Extract Of The Endemic Plant Hammada Scoparia L. From Algeria, Benine Chaima, Djahra Ali Boutlelis, Laiche Ammar Touhami, Tlili Hajer, Tliba Ali, Ben Arfa Abdelkarim, Najjaa Hanen

Karbala International Journal of Modern Science

This study aimed to analyze the chemical profile and evaluate the biological activities of the aqueous extract of H. Scoparia, an endemic plant found in Southeastern Algeria. The aqueous extract was subjected to phytochemical screening, RP-HPLC, and FT-IR analysis. The anti-inflammatory activity was examined using the protein denaturation method, and the photoprotective activity was evaluated using UV-Visible spectrophotometry. The antioxidant activity was assessed using ABTS, DPPH, and FRAP assays. The study found the presence of various secondary metabolites such as polyphenols, tannins, and saponins. This study suggests that H. Scoparia extract has the potential as a natural source of bio-actives …

Mpla Case: How Do You Lead As A Lead Physicist?, Patricia Sansourekidou, Leonard Kim, Lee Xu, Mary Gronberg, Cassandra Stambaugh, Dongxu Wang

Faculty, Staff and Student Publications

This work of fiction is part of a case study series developed by the Medical Physics Leadership Academy (MPLA). It is intended to facilitate the discussion of the managerial and leadership challenges faced by a clinical medical physicist. In this case, a physicist David used to work in a clinic where he thrived and felt like a leader, despite not having the title. After a job change, he is now officially the "Lead Physicist" at a hospital newly affiliated with a large academic healthcare system. He believes he will be equally successful. Yet he struggles to bring about changes and …

Out-Of-Distribution Generalization Of Deep Learning To Illuminate Dark Protein Functional Space, Tian Cai

Dissertations, Theses, and Capstone Projects

Dark protein illumination is a fundamental challenge in drug discovery where majority human proteins are understudied, i.e. with only known protein sequence but no known small molecule binder. It's a major road block to enable drug discovery paradigm shift from single-targeted which looks to identify a single target and design drug to regulate the single target to multi-targeted in a Systems Pharmacology perspective. Diseases such as Alzheimer's and Opioid-Use-Disorder plaguing millions of patients call for effective multi-targeted approach involving dark proteins. Using limited protein data to predict dark protein property requires deep learning systems with OOD generalization capacity. Out-of-Distribution (OOD) …

Optimization And Application Of Graph Neural Networks, Shuo Zhang

Dissertations, Theses, and Capstone Projects

Graph Neural Networks (GNNs) are widely recognized for their potential in learning from graph-structured data and solving complex problems. However, optimal performance and applicability of GNNs have been an open-ended challenge. This dissertation presents a series of substantial advances addressing this problem. First, we investigate attention-based GNNs, revealing a critical shortcoming: their ignorance of cardinality information that impacts their discriminative power. To rectify this, we propose Cardinality Preserved Attention (CPA) models that can be applied to any attention-based GNNs, which exhibit a marked improvement in performance. Next, we introduce the Directional Node Pair (DNP) descriptor and the Robust Molecular Graph …

Syne1 Mutation Is Associated With Increased Tumor Mutation Burden And Immune Cell Infiltration In Ovarian Cancer, Laura M. Harbin, Nan Lin, Frederick R. Ueland, Jill M. Kolesar

Markey Cancer Center Faculty Publications

SYNE1, a nuclear envelope protein critical for cellular structure and signaling, is downregulated in numerous malignancies. SYNE1 alterations are found in 10% of gynecologic malignancies and 5% of epithelial ovarian cancers. Previous studies demonstrated an association between SYNE1 mutation, increased tumor mutation burden (TMB), and immunotherapy response. This study evaluates the SYNE1 mutation frequency, association with TMB, and downstream effects of SYNE1 mutation in ovarian cancer. Genetic information, including whole-exome sequencing, RNA analysis, and somatic tumor testing, was obtained for consenting ovarian cancer patients at an academic medical center. Mutation frequencies were compared between the institutional cohort and The Cancer …