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Cellular And Molecular Mechanisms Underlying Alcohol-Induced Aggressiveness Of Breast Cancer, Yongchao Wang, Mei Xu, Zun-Ji Ke, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Breast cancer is a leading cause of morbidity and mortality in women. Both Epidemiological and experimental studies indicate a positive correlation between alcohol consumption and the risk of breast cancer. While alcohol exposure may promote the carcinogenesis or onset of breast cancer, it may as well enhance the progression and aggressiveness of existing mammary tumors. Recent progress in this line of research suggests that alcohol exposure is associated with invasive breast cancer and promotes the growth and metastasis of mammary tumors. There are multiple potential mechanisms involved in alcohol-stimulated progression and aggressiveness of breast cancer. Alcohol may increase the mobility …

Endoplasmic Reticulum Stress And Inflammation In The Central Nervous System, Neil T. Sprenkle, Savannah G. Sims, Cristina L. Sánchez, Gordon P. Meares

Faculty & Staff Scholarship

Persistent endoplasmic reticulum (ER) stress is thought to drive the pathology of many chronic disorders due to its potential to elicit aberrant inflammatory signaling and facilitate cell death. In neurodegenerative diseases, the accumulation of misfolded proteins and concomitant induction of ER stress in neurons contributes to neuronal dysfunction. In addition, ER stress responses induced in the surrounding neuroglia may promote disease progression by coordinating damaging inflammatory responses, which help fuel a neurotoxic milieu. Nevertheless, there still remains a gap in knowledge regarding the cell-specific mechanisms by which ER stress mediates neuroinflammation. In this review, we will discuss recently uncovered inflammatory …

Acute Temporal Changes Of Mri-Tracked Tumor Vascular Parameters After Combined Anti-Angiogenic And Radiation Treatments In A Rat Glioma Model: Identifying Signatures Of Synergism, Rasha Elmghirbi, Tavarekere N. Nagaraja, Stephen L. Brown, Swayamprava Panda, Madhava P. Aryal, Kelly A. Keenan, Hassan Bagher-Ebadian, Glauber Cabral, James R. Ewing

Neurology Articles

In this study we used magnetic resonance imaging (MRI) biomarkers to monitor the acute temporal changes in tumor vascular physiology with the aim of identifying the vascular signatures that predict response to combined anti-angiogenic and radiation treatments. Forty-three athymic rats implanted with orthotopic U-251 glioma cells were studied for approximately 21 days after implantation. Two MRI studies were performed on each animal, pre- and post-treatment, to measure tumor vascular parameters. Two animal groups received treatment comprised of Cilengitide, an anti-angiogenic agent and radiation. The first group received a subcurative regimen of Cilengitide 1 h before irradiation, while the second group …

The Application Of Mesenchymal Progenitor Stem Cells For The Reduction Of Oxidative Stress In Animals, Edyta Wojtas, Andrzej Zachwieja, Anna Zwyrzykowska, Robert Kupczynski, Krzysztof Marycz

Turkish Journal of Biology

Oxidative stress is the primary cause of lowering of the body's immune status. It arises as a result of intense metabolic processes in humans and animals that involve a decrease in antioxidant enzymes activity at the expense of increased production of free radicals and reactive oxygen species (ROS). Consequently, this leads to oxidation of lipids, proteins, DNA, and RNA, causing cell proliferation reduction, faster cell aging, and subsequent degradation. Currently, there is a search for methods to maintain an oxidation-antioxidant balance. The results of many authors' research point to the effectiveness of the use of mesenchymal stem cells (MSCs) in …

Novel Evidence That The Mannan-Binding Lectin Pathway Of Complement Activation Plays A Pivotal Role In Triggering Mobilization Of Hematopoietic Stem/Progenitor Cells By Activation Of Both The Complement And Coagulation Cascades, M. Adamiak, A. Abdelbaset-Ismail, M. Suszynska, Ahmed K. Abdel-Latif, J. Ratajczak, M. Z. Ratajczak

Internal Medicine Faculty Publications

No abstract provided.

Ligand Trap Of The Activin Receptor Type Iia Inhibits Osteoclast Stimulation Of Bone Remodeling In Diabetic Mice With Chronic Kidney Disease, Toshifumi Sugatani, Olga A. Agapova, Yifu Fang, Alycia G. Berman, Joseph M. Wallace, Hartmut H. Malluche, Marie-Claude Faugere, William Smith, Victoria Sung, Keith A. Hruska

Internal Medicine Faculty Publications

Dysregulation of skeletal remodeling is a component of renal osteodystrophy. Previously, we showed that activin receptor signaling is differentially affected in various tissues in chronic kidney disease (CKD). We tested whether a ligand trap for the activin receptor type 2A (RAP-011) is an effective treatment of the osteodystrophy of the CKD-mineral bone disorder. With a 70% reduction in the glomerular filtration rate, CKD was induced at 14 weeks of age in the ldlr−/− high fat-fed mouse model of atherosclerotic vascular calcification and diabetes. Twenty mice with CKD, hyperphosphatemia, hyperparathyroidism, and elevated activin A were treated with RAP-011, wherease 19 …

Multiple Targets For Novel Therapy Of Fsgs Associated With Circulating Permeability Factor., Virginia J. Savin, Mukut Sharma, Jianping Zhou, David Genochi, Ram Sharma, Tarak Srivastava, Amna Ilahe, Pooja Budhiraja, Aditi Gupta, Ellen T. Mccarthy

Manuscripts, Articles, Book Chapters and Other Papers

A plasma component is responsible for altered glomerular permeability in patients with focal segmental glomerulosclerosis. Evidence includes recurrence after renal transplantation, remission after plasmapheresis, proteinuria in infants of affected mothers, transfer of proteinuria to experimental animals, and impaired glomerular permeability after exposure to patient plasma. Therapy may include decreasing synthesis of the injurious agent, removing or blocking its interaction with cells, or blocking signaling or enhancing cell defenses to restore the permeability barrier and prevent progression. Agents that may prevent the synthesis of the permeability factor include cytotoxic agents or aggressive chemotherapy. Extracorporeal therapies include plasmapheresis, immunoadsorption with protein A …

Biochemical And Biophysical Methods For Analysis Of Poly(Adp-Ribose) Polymerase 1 And Its Interactions With Chromatin., Maggie H. Chassé, Uma M. Muthurajan, Nicholas J. Clark, Michael A. Kramer, Srinivas Chakravarthy, Thomas Irving, Karolin Luger

Manuscripts, Articles, Book Chapters and Other Papers

Poly (ADP-Ribose) Polymerase I (PARP-1) is a first responder to DNA damage and participates in the regulation of gene expression. The interaction of PARP-1 with chromatin and DNA is complex and involves at least two different modes of interaction. In its enzymatically inactive state, PARP-1 binds native chromatin with similar affinity as it binds free DNA ends. Automodification of PARP-1 affects interaction with chromatin and DNA to different extents. Here we describe a series of biochemical and biophysical techniques to quantify and dissect the different binding modes of PARP-1 with its various substrates. The techniques listed here allow for high …

The Impact Of Sglt2 Inhibitors, Compared With Insulin, On Diabetic Bone Disease In A Mouse Model Of Type 1 Diabetes, Kathryn M. Thrailkill, Jeffry S. Nyman, R. Clay Bunn, Sasidhar Uppuganti, Katherine L. Thompson, Charles K. Lumpkin, Evangelia Kalaitzoglou, John L. Fowlkes

Barnstable Brown Diabetes Center Faculty Publications

Skeletal co-morbidities in type 1 diabetes include an increased risk for fracture and delayed fracture healing, which are intertwined with disease duration and the presence of other diabetic complications. As such, chronic hyperglycemia is undoubtedly a major contributor to these outcomes, despite standard insulin-replacement therapy. Therefore, using the streptozotocin (STZ)-induced model of hypoinsulinemic hyperglycemia in DBA/2J male mice, we compared the effects of two glucose lowering therapies on the fracture resistance of bone and markers of bone turnover. Twelve week-old diabetic (DM) mice were treated for 9 weeks with: 1) oral canagliflozin (CANA, dose range ~10-16 mg/kg/day), an inhibitor of …

Captive: Zoometric Operations In Gaza, Irus Braverman

Journal Articles

“We are the only people in this world who are living under such total occupation. Israel sees us as being equal to our animals, and sometimes they even value us less than our animals.” This quote, from the founder of the Gaza Zoo, demonstrates both the significance and the complexities of human-animal relations in Gaza, especially at times of siege and war. My article draws on ethnographic encounters and investigative analysis to relay how Gaza’s spatial confinement generally, and the Israeli incursion into Gaza of summer 2014 in particular, has lent itself to a radicalized discursive interplay between the animalization …

Mc-Ppea As A New And More Potent Inhibitor Of Clp-Induced Sepsis And Pulmonary Inflammation Than Fk866., Peixin Huang, Mark W Lee, Keivan Sadrerafi, Daniel P. Heruth, Li Q. Zhang, Dev Maulik, Shui Qing Ye

Manuscripts, Articles, Book Chapters and Other Papers

Our previous study indicated that overexpression of nicotinamide phosphoribosyltransferase (NAMPT) aggravated acute lung injury, while knockdown of NAMPT expression attenuated ventilator-induced lung injury. Recently, we found that meta-carborane-butyl-3-(3-pyridinyl)-2E-propenamide (MC-PPEA, MC4), in which the benzoylpiperidine moiety of FK866 has been replaced by a carborane, displayed a 100-fold increase in NAMPT inhibition over FK866. Here, we determined the effects of MC4 and FK866 on cecal ligation and puncture (CLP) surgery-induced sepsis in C57BL/6J mice. MC4 showed stronger inhibitory effects than FK866 on CLP-induced mortality, serum tumor necrosis factor α (TNFα) levels, pulmonary myeloperoxidase activity, alveolar injury, and interleukin 6 and interleukin1β messenger …

Altered Gut Microbiome In A Mouse Model Of Gulf War Illness Causes Neuroinflammation And Intestinal Injury Via Leaky Gut And Tlr4 Activation, Firas Alhasson, Suvarthi Das, Ratanesh K. Seth, Diptadip Dattaroy, Varun Chandrashekaran, Caitlin N. Ryan, Luisa S. Chan, Traci Testerman, James Burch, Lorne J. Hofseth, Ronnie Horner, Mitzi Nagarkatti, Prakash Nagarkatti, Stephen M. Lasley, Saurabh Chatterjee

Faculty Publications

Many of the symptoms of Gulf War Illness (GWI) that include neurological abnormalities, neuroinflammation, chronic fatigue and gastrointestinal disturbances have been traced to Gulf War chemical exposure. Though the association and subsequent evidences are strong, the mechanisms that connect exposure to intestinal and neurological abnormalities remain unclear. Using an established rodent model of Gulf War Illness, we show that chemical exposure caused significant dysbiosis in the gut that included increased abundance of phylum Firmicutes and Tenericutes, and decreased abundance of Bacteroidetes. Several gram negative bacterial genera were enriched in the GWI-model that included Allobaculum sp. Altered microbiome caused significant decrease …

Animal Welfare: Measuring Strategies For Improving Lives, Elsbeth Paige-Jeffers Ma

All Student Scholarship

Animals are sentient creatures entitled to humane treatment and lives of dignity. There are many fields which address this notion, including animal welfare science, ethics, law, policy, and veterinary science. Such a multi-disciplinary approach to animal welfare reveals numerous best practices which can be used to improve the way animals are conceived of and treated by both specialists and the public. However, despite this faceted consideration of animal welfare, there is a dearth of quantitative means to assess entities’ adherence to best practices. As such, the purpose of present study is to develop and refine an instrument which could be …

Targeted Calcium Influx Boosts Cytotoxic T Lymphocyte Function In The Tumour Microenvironment, Kyun-Do Kim, Seyeon Bae, Tara Capece, Hristina Nedelkovska, Rafael G. De Rubio, Alan V. Smrcka, Jun Chang-Duk, Jung Woojin, Byeonghak Park, Minsoo Kim, Tae-Il Kim, Minsoo Kim

Biology

Adoptive cell transfer utilizing tumour-targeting cytotoxic T lymphocytes (CTLs) is one of the most effective immunotherapies against haematological malignancies, but significant clinical success has not yet been achieved in solid tumours due in part to the strong immunosuppressive tumour microenvironment. Here, we show that suppression of CTL killing by CD4+CD25+Foxp+ regulatory T cell (Treg) is in part mediated by TGFβ-induced inhibition of inositol trisphosphate (IP3) production, leading to a decrease in T cell receptor (TCR)-dependent intracellular Ca2+ response. Highly selective optical control of Ca2+ signalling in adoptively transferred CTLs enhances T cell activation and IFN-γ production in vitro, leading to …

Animal Sentience? Neuroscience Has No Answers, Yoram Gutfreund

Animal Sentience

Woodruff’s target article provides a detailed review of comparative studies on brain and behavior in teleosts. However, the relevance of the scientific data to the question of consciousness rests solely on the validity of a small set of so-called "requirements for consciousness." I use the target article to demonstrate that the neuroscientific study of animal consciousness in general relies on external, highly questionable and unfalsifiable criteria, and therefore fails to resolve the question of which animal species are sentient. Fish behavior can be remarkably complex, but whether fish are conscious remains a matter of belief.

Seasonal And Regional Animal Use Of Drainage Structures To Cross Under Roadways, James L. Sparks, J. Edward Gates

Human–Wildlife Interactions

Road drainage structures, hereafter designated culverts, are often used by wildlife and other animals to cross under roadways. However, crossings may vary by species, culvert design, different environmental factors, and land-use and land-cover (LULC) at culvert sites. We monitored 265 culverts located throughout Maryland, USA, with motion-detecting game cameras to assess seasonal and regional effects on culvert crossing rates by wildlife and other animal species considered common to the areas. Northern raccoon (Procyon lotor) and Virginia opossum (Didelphis virginiana) exhibited lower crossing rates in culverts during winter than at other times of the year. We did not detect any difference …

Comparative Proteomic Analyses Of The Parietal Lobe From Rhesus Monkeys Fed A High-Fat/Sugar Diet With And Without Resveratrol Supplementation, Relative To A Healthy Diet: Insights Into The Roles Of Unhealthy Diets And Resveratrol On Function, Aaron M. Swomley, Judy C. Triplett, Jeriel T. Keeney, Govind Warrier, Kevin J. Pearson, Julie A. Mattison, Rafael De Cabo, Jian Cai, Jon B. Klein, D. Allan Butterfield

Chemistry Faculty Publications

A diet consisting of a high intake of saturated fat and refined sugars is characteristic of a Western-diet and has been shown to have a substantial negative effect on human health. Expression proteomics were used to investigate changes to the parietal lobe proteome of rhesus monkeys consuming either a high fat and sugar (HFS) diet, a HFS diet supplemented with resveratrol (HFS+RSV), or a healthy control diet for 2 years. Here we discuss the modifications in the levels of 12 specific proteins involved in various cellular systems including metabolism, neurotransmission, structural integrity, and general cellular signaling following a nutritional intervention. …

Aav-Mediated Expression Of Anti-Tau Scfvs Decreases Tau Accumulation In A Mouse Model Of Tauopathy, Christina Ising, Gilbert Gallardo, Cheryl E.G. Leyns, Connie H. Wong, Hong Jiang, Floy Stewart, Lauren J. Koscal, Joseph Roh, Grace O. Robinson, Javier Remolina Serrano, David M. Holtzman

Open Access Publications

Tauopathies are characterized by the progressive accumulation of hyperphosphorylated, aggregated forms of tau. Our laboratory has previously demonstrated that passive immunization with an anti-tau antibody, HJ8.5, decreased accumulation of pathological tau in a human P301S tau-expressing transgenic (P301S-tg) mouse model of frontotemporal dementia/tauopathy. To investigate whether the F

Harnessing The Power Of Cell Transplantation To Target Respiratory Dysfunction Following Spinal Cord Injury., Brittany A. Charsar, Mark W. Urban, Angelo C. Lepore

Department of Neuroscience Faculty Papers

The therapeutic benefit of cell transplantation has been assessed in a host of central nervous system (CNS) diseases, including disorders of the spinal cord such as traumatic spinal cord injury (SCI). The promise of cell transplantation to preserve and/or restore normal function can be aimed at a variety of therapeutic mechanisms, including replacement of lost or damaged CNS cell types, promotion of axonal regeneration or sprouting, neuroprotection, immune response modulation, and delivery of gene products such as neurotrophic factors, amongst other possibilities. Despite significant work in the field of transplantation in models of SCI, limited attention has been directed at …

Effect Of Pulse Shaping On Subharmonic Aided Pressure Estimation In Vitro And In Vivo., Ipshita Gupta, John R. Eisenbrey, Maria Stanczak, Anush Sridharan, Jaydev K. Dave, Ji-Bin Liu, Christopher Hazard, Xinghua Wang, Ping Wang, Huiwen Li, Kirk Wallace, Flemming Forsberg

Department of Radiology Faculty Papers

OBJECTIVES: Subharmonic imaging (SHI) is a technique that uses the nonlinear oscillations of microbubbles when exposed to ultrasound at high pressures transmitting at the fundamental frequency ie, f

METHODS: Eight waveforms with different envelopes were optimized with respect to acoustic power at which the SHAPE study is most sensitive. The study was run with four input transmit cycles, first in vitro and then in vivo in three canines to select the waveform that achieved the best sensitivity for detecting changes in portal pressures using SHAPE. A Logiq 9 scanner with a 4C curvi-linear array was used to acquire 2.5 MHz …

Targeting The Nrf2-Heme Oxygenase-1 Axis After Intracerebral Hemorrhage., Jing Chen-Roetling, Raymond F. Regan

Department of Emergency Medicine Faculty Papers

BACKGROUND: Injury to cells adjacent to an intracerebral hemorrhage (ICH) is likely mediated at least in part by toxins released from the hematoma that initiate complex and interacting injury cascades. Pharmacotherapies targeting a single toxin or pathway, even if consistently effective in controlled experimental models, have a high likelihood of failure in a variable clinical setting. Nuclear factor erythroid-2 related factor 2 (Nrf2) regulates the expression of heme oxygenase-1 (HO-1) and multiple other proteins with antioxidant and antiinflammatory effects, and may be a target of interest after ICH.

METHODS: Studies that tested the effect of HO and Nrf2 in models …

Adiponectin Partially Rescues High Glucose/High Fat-Induced Impairment Of Mitochondrial Biogenesis And Function In A Pgc-1Α Dependent Manner., H. Wang, W.-J. Yan, J.-L. Zhang, F.-Y. Zhang, C. Gao, Y.-J. Wang, W.B. Lau, L. Tao

Department of Emergency Medicine Faculty Papers

OBJECTIVE: Plasma adiponectin (APN) levels are decreased in diabetic patients. Dysfunctional mitochondrial biogenesis is involved in type 2 diabetes (T2DM) pathogenesis, by unclear mechanisms. The present study determined (1) whether myocardial mitochondrial biogenesis was impaired in cardiomyocytes exposed to a high glucose/high fat (HGHF) medium (a T2DM in vitro model), (2) the effects of APN administration upon mitochondrial biogenesis in cardiomyocytes affected by HGHF incubation, and 3) the involved underlying mechanisms.

MATERIALS AND METHODS: Neonatal rat ventricular myocytes (NRVMs) were isolated and incubated in HGHF medium. Mitochondrial function was assessed by ATP content, and fluorescent microscopic analysis of myocardial apoptosis …

After;Life, Morgan Lynn Anderson

LSU Master's Theses

After;life is an exploration of the time and space between life and death. The installation, created from dozens of woodcut prints, creates this imaginary place, and encompasses viewers through sight, smell, sound, and touch. All elements of this installation are heavily influenced by Southern Louisiana culture and wildlife, and are meant to be familiar enough to provoke personal memory and experience. A set of rituals in the form of three poems, corresponding to three different spirit guides: The Black Dog, The Alligator, and The Opossum, lead the reader through the space from life, through liminal, into death.

Similar Adverse Events From Two Disparate Agents Implicate Lipid Inflammatory Mediators For A Role In Anxiety States, Gordon Mccarter, Lauren B. Blanchard

Faculty Publications & Research of the TUC College of Pharmacy

We recently reported a case in which a 54-year-old male experienced maintenance insomnia, generalized anxiety and panic symptoms associated with consumption of a fish oil supplement enriched in eicosapentaenoic acid (EPA). We report here that the same patient has experienced identical but more severe symptoms in response to the use of the leukotriene receptor antagonist montelukast, in accordance with other cases reported to the Food and Drug Administration. Since omega-3 fatty acids like EPA are precursors for the biosynthesis of eicosanoids including leukotrienes, a common factor to these psychiatric adverse events may be perturbations in this highly complex system of …

Fibroblast Growth Requires Ct10 Regulator Of Kinase (Crk) And Crk-Like (Crkl)., Taeju Park, Mateusz Koptyra, Tom Curran

Manuscripts, Articles, Book Chapters and Other Papers

CT10 regulator of kinase (Crk) and Crk-like (CrkL) are the cellular counterparts of the viral oncogene v-Crk Elevated levels of Crk and CrkL have been observed in many human cancers; inhibition of Crk and CrkL expression reduced the tumor-forming potential of cancer cell lines. Despite a close relationship between the Crk family proteins and tumorigenesis, how Crk and CrkL contribute to cell growth is unclear. We ablated endogenous Crk and CrkL from cultured fibroblasts carrying floxed alleles of Crk and CrkL by transfection with synthetic Cre mRNA (synCre). Loss of Crk and CrkL induced by synCre transfection blocked cell proliferation …

Selective Suppression Of The Α Isoform Of P38 Mapk Rescues Late-Stage Tau Pathology, Nicole Maphis, Shanya Jiang, Guixiang Xu, Olga N. Kokiko-Cochran, Saktimayee M. Roy, Linda J. Van Eldik, D. Martin Watterson, Bruce T. Lamb, Kiran Bhaskar

Sanders-Brown Center on Aging Faculty Publications

Background: Hyperphosphorylation and aggregation of tau protein are the pathological hallmarks of Alzheimer’s disease and related tauopathies. We previously demonstrated that the microglial activation induces tau hyperphosphorylation and cognitive impairment via activation of p38 mitogen-activated protein kinase (p38 MAPK) in the hTau mouse model of tauopathy that was deficient for microglial fractalkine receptor CX3CR1.

Method: We report an isoform-selective, brain-permeable, and orally bioavailable small molecule inhibitor of p38α MAPK (MW181) and its effects on tau phosphorylation in vitro and in hTau mice.

Results: First, pretreatment of mouse primary cortical neurons with MW181 completely blocked inflammation-induced p38α MAPK activation and AT8 …

Animals Aren’T Persons, But Is It Time For A Neologism?, Helen Steward

Animal Sentience

Mark Rowlands argues that at least some animals are persons, based on the idea that (i) many animals have a property he calls “pre-reflective awareness,” (ii) the capacity for pre-reflective awareness is sufficient to satisfy the traditional Lockean definition of personhood, and (iii) satisfaction of the traditional Lockean definition of personhood is sufficient for being a person. I agree with (i) and can see that there is a persuasive case for (ii), but I think the case against (iii) blocks the conclusion that animals are persons. I suggest that we may need instead to coin a neologism in order to …

A Hundred Horses, Cynthia Frazier

Children's Book and Media Review

Eleven year old Nell leads a very busy life full of classes and clubs that she hates. Now she is being forced to spend her spring break in the country with an aunt she can’t remember and two small cousins she doesn’t even want to get to know. On top of that, a suitcase containing a special project has been stolen by someone riding a big black and white horse. Somewhere between Maggie the pig having piglets, rescuing flying chickens, and tracking down a missing goat Nell meets an unlikely friend in a girl named Angel. People say that Angel …

There's A Giraffe In My Soup, Aylea Stephens

Children's Book and Media Review

One boy has terrible luck in a restaurant when animals keep ending up in his soup! First it’s a giraffe, but even after he gets a fresh bowl of soup, the new bowl has an alligator in it. It’s followed by an elephant that can’t swim, a yak, walrus, and many other animals as the boy and the waiter try to get a bowl of soup that the boy can eat without any animals in it. When the waiter gets tired of the boy’s complaints, they finally discover why there are so many animals in the soup.

Chicken In Space, Lori Cunningham

Children's Book and Media Review

Zoey an adventurous chicken and her best friend Sam, the pie loving pig, take you on amazing journey through the power of imagination. Zoey, determined to make her voyage into space, formulates a plan with her sidekick Sam to explore the great skies above. Throughout the book her other farmyard friends have doubts, but Zoey and Sam are determined to find a way and turn their problems into an opportunity. Zoey and Sam make everyday items into something extraordinary: a spaceship, asteroids, comets, and more. Once back at the barnyard, Sam--still hoping for pie--tells all their friends of the adventure …