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Targeting Mitochondria In Cancer Therapy Could Provide A Basis For The Selective Anticancer Activity, Dmitri Rozanov, Anton Cheltsov, Aaron Nilsen, Christopher Boniface, Isaac Forquer, James Korkola, Joe Gray, Multiple Additional Authors

Chemistry Faculty Publications and Presentations

To determine the target of the recently identified lead compound NSC130362 that is responsible for its selective anti-cancer efficacy and safety in normal cells, structure-activity relationship (SAR) studies were conducted. First, NSC13062 was validated as a starting compound for the described SAR studies in a variety of cell-based viability assays. Then, a small library of 1,4-naphthoquinines (1,4-NQs) and quinoline-5,8-diones was tested in cell viability assays using pancreatic cancer MIA PaCa-2 cells and normal human hepatocytes. The obtained data allowed us to select a set of both non-toxic compounds that preferentially induced apoptosis in cancer cells and toxic compounds that induced …

Methods For Monitoring Matrix-Induced Autophagy., Carolyn Chen, Aastha Kapoor, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

A growing body of research demonstrates modulation of autophagy by a variety of matrix constituents, including decorin, endorepellin, and endostatin. These matrix proteins are both pro-autophagic and anti-angiogenic. Here, we detail a series of methods to monitor matrix-induced autophagy and its concurrent effects on angiogenesis. We first discuss cloning and purifying proteoglycan fragment and core proteins in the laboratory and review relevant techniques spanning from cell culture to treatment with these purified proteoglycans in vitro and ex vivo. Further, we cover protocols in monitoring autophagic progression via morphological and microscopic characterization, biochemical western blot analysis, and signaling pathway investigation. Downstream …

Female Sex And Cardiovascular Disease Risk In Rural Uganda: A Cross-Sectional, Population-Based Study, Itai M. Magodoro, Maggie Feng, Crystal North, Dagmar Vořechovská, John D. Kraemer, Bernard Kakuhikire, David Bangsberg, Alexander C. Tsai, Mark J. Siedner

OHSU-PSU School of Public Health Faculty Publications and Presentations

Background:

Sex-based differences in cardiovascular disease (CVD) burden are widely acknowledged, with male sex considered a risk factor in high-income settings. However, these relationships have not been examined in sub- Saharan Africa (SSA). We aimed to apply the American Heart Association (AHA) ideal cardiovascular health (CVH) tool modified by the addition of C-reactive protein (CRP) to examine potential sex-based differences in the prevalence of CVD risk in rural Uganda.

Methods: In a cross-sectional study nested within a population-wide census, 857 community-living adults completed physical and laboratory-based assessments to calculate individual ideal CVH metrics including an eight category for CRP levels. …

A Proof-Of-Mechanism Study To Test Effects Of The Nmda Receptor Antagonist Lanicemine On Behavioral Sensitization In Individuals With Symptoms Of Ptsd, Marijn Lijffijt, Charles E Green, Nicholas Balderston, Tabish Iqbal, Megan Atkinson, Brittany Vo-Le, Bylinda Vo-Le, Brittany O'Brien, Christian Grillon, Alan C Swann, Sanjay J Mathew

Faculty, Staff and Students Publications

Background: Individuals with post-traumatic stress disorder (PTSD) have a heightened sensitivity to subsequent stressors, addictive drugs, and symptom recurrence, a form of behavioral sensitization. N-methyl-D-aspartate receptors (NMDARs) are involved in the establishment and activation of sensitized behavior.

Objective: We describe a protocol of a randomized placebo-controlled Phase 1b proof-of-mechanism trial to examine target engagement, safety, tolerability, and possible efficacy of the NMDAR antagonist lanicemine in individuals with symptoms of PTSD (Clinician Administered PTSD Scale [CAPS-5] score ≥ 25) and evidence of behavioral sensitization measured as enhanced anxiety-potentiated startle (APS; T-score ≥ 2.8).

Methods: Subjects (n = 24; age range 21–65) …

Treatment Of Nightmares In Psychiatric Inpatients With Imagery Rehearsal Therapy: An Open Trial And Case Series, Thomas E Ellis, Katrina A Rufino, Michael R Nadorff

Staff and Researcher Publications

Objectives: This study sought to assess the utility of Imagery Rehearsal Therapy (IRT) for nightmares in an inpatient psychiatric setting. Although IRT enjoys a substantial evidence base for efficacy in various populations, data with psychiatric inpatients are lacking.

Participants: Participants were 20 adult psychiatric inpatients (11 male, 9 female; mean age=43.4), in an extended stay psychiatric inpatient facility. All participants were diagnosed with multiple, treatment resistant, comorbid conditions, including mood disorders, anxiety disorders, personality disorders, and substance-related disorders. Patients with active psychosis or significant cognitive impairment were excluded.

Methods: This was an open trial utilizing a case series design. In …

Sonic Hedgehog Is Expressed By Hilar Mossy Cells And Regulates Cellular Survival And Neurogenesis In The Adult Hippocampus, Luis E. Gonzalez-Reyes, Chia-Chu Chiang, Mingming Zhang, Joshua Johnson, Manuel Arrillaga-Tamez, Nicholas H. Couturier, Neha Reddy, Lev Starikov, Jeffrey R. Capadona, Andreas H. Kottmann, Dominique M. Durand

Publications and Research

Sonic hedgehog (Shh) is a multifunctional signaling protein governing pattern formation, proliferation and cell survival during embryogenesis. In the adult brain, Shh has neurotrophic function and is implicated in hippocampal neurogenesis but the cellular source of Shh in the hippocampus remains ill defined. Here, we utilize a gene expression tracer allele of Shh (Shh-nlacZ) which allowed the identification of a subpopulation of hilar neurons known as mossy cells (MCs) as a prominent and dynamic source of Shh within the dentate gyrus. AAV-Cre mediated ablation of Shh in the adult dentate gyrus led to a marked degeneration …

An Ensemble Of Flexible Conformations Underlies Mechanotransduction By The Cadherin–Catenin Adhesion Complex, Martin Bush, Bashir M. Alhanshali, Shuo Qian, Christopher B. Stanley, William T. Heller, Tsutomu Matsui, Thomas M. Weiss, Iain D. Nicholl, Thomas Walz, David J. E. Callaway, Zimei Bu

Publications and Research

The cadherin–catenin adhesion complex is the central component of the cell–cell adhesion adherens junctions that transmit mechanical stress from cell to cell. We have determined the nanoscale structure of the adherens junction complex formed by the α-catenin•β-catenin•epithelial cadherin cytoplasmic domain (ABE) using negative stain electron microscopy, small-angle X-ray scattering, and selective deuteration/small-angle neutron scattering. The ABE complex is highly pliable and displays a wide spectrum of flexible structures that are facilitated by protein-domain motions in α- and β-catenin. Moreover, the 107-residue intrinsically disordered N-terminal segment of β-catenin forms a flexible “tongue” that is inserted into α-catenin and participates in the …

A Systems Thinking Approach For Eliciting Mental Models From Visual Boundary Objects In Hydropolitical Contexts: A Case Study From The Pilcomayo River Basin, Riveraine S. Walters, Erin S. Kenzie, Alexander E. Metzger, William Jesse Baltutis, Kakali B. Chakrabarti, Shana Lee Hirsch, Bethany Laursen

Complex Systems Faculty Publications and Presentations

Transboundary collaborations related to international freshwater are critical for ensuring equitable, efficient, and sustainable shared access to our planet’s most fundamental resources. Visual artifacts, such as knowledge maps, functioning as boundary objects, are used in hydropolitical contexts to convey understandings and facilitate discussion across scales about challenges and opportunities from multiple perspectives. Such focal points for discussion are valuable in creating shared, socially negotiated priorities and integrating diverse and often disparate cultural perspectives that naturally exist in the context of international transboundary water resources. Visual boundary objects can also represent the collective mental models of the actor countries and transboundary …

Protocol For A Longitudinal Study To Evaluate The Use Of Tenofovir-Based Prep For Safer Conception And Pregnancy Among Women In South Africa, Lynn T. Matthews, Manjeetha Jaggernath, Yolandie Kriel, Patricia Smith, Kasey O’Neil, David Bangsberg, Multiple Additional Authors

OHSU-PSU School of Public Health Faculty Publications and Presentations

Introduction Women who choose to conceive a baby with a partner living with HIV or a partner whose HIV serostatus is unknown in HIV-endemic settings need prevention strategies to mitigate HIV acquisition during conception and pregnancy.

Methods and analysis We are conducting a single-arm longitudinal study offering oral tenofovirdisoproxil fumarate/emtricitabine (TDF/FTC) as pre-exposure prophylaxis (PrEP) for periconception use to 350 HIV-uninfected women in KwaZulu-Natal, South Africa. PrEP is offered as part of woman-centred safer conception programme that promotes couples-based HIV counselling and testing, antiretroviral therapy for partners who are HIV-infected, treatment for sexually transmitted infections and safer conception strategies, such …

Table Of Contents

Journal of the South Carolina Academy of Science

No abstract provided.

Ribonucleotide Reductase Inhibitor 3-Ap Induces Oncogenic Virus Infected Cell Death And Represses Tumor Growth, Lu Dai, Jungang Chen, Yueyu Cao, Luis Del Valle, Zhiqiang Qin

School of Medicine Faculty Publications

Kaposi's Sarcoma-associated Herpesvirus (KSHV) is the etiologic agent of several human malignancies, particularly Kaposi's Sarcoma (KS), which preferentially arise in immunocompromised patients such as HIV+ subpopulation while still lacking of effective therapeutic options. We recently found that the ribonucleotide reductase (RR) subunit M2 is potentially regulated by the key oncogenic HGF/c-MET pathway in KSHV-related lymphoma cells. One of RR inhibitor, 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) effectively induced apoptosis of KSHV+ lymphomas and suppressed tumor progression . In the current study, we found that 3-AP treatment selectively inhibited the proliferation of KSHV-infected endothelial cells, the major cellular components of KS, through inducing DNA …

Effect Of Pulsed Electromagnetic Field On Menstrual Distress In Primary Dysmenorrhic Women, Ahmed H. Abd El Aziz, Engy M. El Nahas, Hesham M. Kamal

Journal of Medicine in Scientific Research

Background Primary dysmenorrhea is a common menstrual cramp that is recurrent and is not owing to other diseases and is a common cause of stay at home and school or work. Purpose The purpose of this study was to investigate the effect of pulsed electromagnetic field (PEMF) on menstrual distress in primary dysmenorrheic women. Patients and methods A total of 40 women having primary dysmenorrhea were selected from Physical Therapy Department in Al Mataria Teaching Hospital in Cairo. Their ages ranged from 20 to 30 years. They were divided randomly into two groups equal in number: group A (study group), …

Comparison Between The Effect Of Intra-Articular Injections Of Platelet-Rich Plasma And Corticosteroids In Advanced Knee Osteoarthritis, Abeer H. Ismaiel

Journal of Medicine in Scientific Research

Objective The objective of this study was to compare intra-articular injections (IAIs) of platelet-rich plasma (PRP) and corticosteroid injections in reducing pain and studying which has a more effective and lasting functional improvement. Patients and methods A total of 60 patients with chronic knee osteoarthritis (Kellgren–Lawrence grades 3 and 4) were enrolled in this study. Patients were randomized to treatment either with a single leukocyte-rich PRP or corticosteroid IAIs. Patients were assessed by visual analog scale, and Knee injury and Osteoarthritis Outcome Score at 1, 3, and 6 months after treatment. Results Our results showed improvement in all variables in …

Laparoscopic Presentation In Unexplained Infertility: A Retrospective Study, Abd Elatif M. Elbalshy, Ashraf M. Kansouh

Journal of Medicine in Scientific Research

Objective Infertility is a growing challenge for all gynecologists worldwide. There is no definite answer as to what should be the best approach to the management of the couples with unexplained infertility (UI). This study aimed to evaluate laparoscopic diagnostic findings that were helpful in planning the protocol for management of cases of UI. Patients and methods This retrospective study was conducted in Shibeen El Kom Teaching Hospital, Egypt, from January 2012 to October 2017. Data of 250 infertile couples were collected from patient case records and subjected to laparoscopy or combined with hysteroscopy. Intraoperative findings such as endometriosis, pelvic …

The Relationship Between Presbycusis And Vestibular Activity, Gehan M. S. Abd El-Salam

Journal of Medicine in Scientific Research

Introduction Presbycusis or age-related sensorineural hearing loss (SNHL) is a complex disorder that results in a slow deterioration in auditory function. A considerably high number of these patients with presbycusis or age-related SNHL also experience dizziness and related vestibular symptoms. Although auditory and vestibular systems are distinct, they work just alike. So, there is a great relation among their functions. Once one is stimulated, the other experiences changes as well. Participants and methods This study comprised 40 adult patients (50–75 years) without any vestibular symptoms or diagnosed vestibular diseases. Audiological status was measured with auditory brainstem response (ABR). The vestibular …

Effects Of Iron-Deficiency Anemia On Auditory Function In School-Aged Children, Eman Soliman Abd El-Gaffar, Gehan M. S. Abd El-Salam, Hala M. Abd El-Samad

Journal of Medicine in Scientific Research

Introduction Iron is important for proper myelination of spinal cord and white matter of cerebellar folds in brain and is a cofactor for a number of enzymes involved in neurotransmitter synthesis. Auditory brainstem evoked response (ABR) represents the progressive activation of different levels of the auditory pathway from the acoustic nerve (wave I) to the lateral lemniscuses (wave V). Otoacoustic emissions (OAEs) are sounds measured in the external ear canal that reflect movement of the outer hair cells in the cochlea. Patients and methods A total of 40 children, of both sexes, with age ranging from 6–12 years old, were …

Screening And Identification Of Red Blood Cell Alloantibodies Among Hemodialysis Patients In National Institute Of Urology And Nephrology, Ahmed Hasan, Aisha M. A. Elshimy, Tarek A. Fouad

Journal of Medicine in Scientific Research

Background It is well known that alloimmunization to red blood cell antigens resulting from the genetic disparities between the donor and the recipient is one of the risks of blood transfusion. Alloimmunization can result in clinical hemolysis and difficulty in cross-matching blood. The risk of alloimmunization is higher in patients who have received multiple blood transfusions such as renal failure patients on dialysis who receive blood transfusions. The antibody-screening test (2–3 cells panel) used to detect unexpected antibodies is not a mandatory pretransfusion testing in our blood bank of National Institute of Urology and Nephrology (NIUN), and is performed routinely …

High Affinity Binding Of H3k14ac Through Collaboration Of Bromodomains 2, 4 And 5 Is Critical For The Molecular And Tumor Suppressor Functions Of Pbrm1., Lili Liao, Nilda L. Alicea-Velázquez, Lauren Langbein, Xiaohua Niu, Weijia Cai, Eun-Ah Cho, Meiling Zhang, Celeste B. Greer, Qin Yan, Michael S. Cosgrove, Haifeng Yang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Polybromo-1 (PBRM1) is an important tumor suppressor in kidney cancer. It contains six tandem bromodomains (BDs), which are specialized structures that recognize acetyl-lysine residues. While BD2 has been found to bind acetylated histone H3 lysine 14 (H3K14ac), it is not known whether other BDs collaborate with BD2 to generate strong binding to H3K14ac, and the importance of H3K14ac recognition for the molecular and tumor suppressor function of PBRM1 is also unknown. We discovered that full-length PBRM1, but not its individual BDs, strongly binds H3K14ac. BDs 2, 4, and 5 were found to collaborate to facilitate strong binding to H3K14ac. Quantitative …

In Vitro Growth Of Human Ovarian Follicles For Fertility Preservation, Diego Marin, Min Yang, Tianren Wang

Department of Biochemistry and Molecular Biology Faculty Papers

Young female cancer survival rates significantly increased due to the great progress of cancer therapy. In fact, cryostorage and transplantation of ovarian tissue have already resulted in the birth of healthy babies. Follicle in vitro growth (IVG) has the great potential of restoring fertility by achieving functional oocytes from the most immature stages to maturation. This is suitable for a wide range of patients, from pubertal to perimenopause women. Notable achievements have been achieved in human follicle IVG in the past decade. Mature oocytes have been successfully collected from long-term sequential follicle IVG. However, it is still a major challenge …

Week Of December 24, 2018, New York Medical College

InTouch

• Department of Surgery Hosts 15th Annual Louis R.M. DelGuercio Distinguished Visiting Professorship and Research Day
• SHSP Hosts Winter Meet and Greet
• GSA Sponsors Third Annual Snowman Project

Efficacy Of A T Cell-Biased Adenovirus Vector As A Zika Virus Vaccine, Brianna L. Bullard, Brigette N. Corder, Matthew J. Gorman, Michael S. Diamond, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Zika virus (ZIKV) is a major public health concern due to the risk of congenital Zika syndrome in developing fetuses and Guillain-Barre syndrome in adults. Currently, there are no approved vaccines available to protect against infection. Adenoviruses are safe and highly immunogenic vaccine vectors capable of inducing lasting humoral and cellular immune responses. Here, we developed two Adenovirus (Ad) vectored Zika virus vaccines by inserting a ZIKV prM-E gene expression cassette into human Ad types 4 (Ad4-prM-E) and 5 (Ad5-prM-E). Immune correlates indicate that Ad5-prM-E vaccination induces both an anti-ZIKV antibody and T-cell responses whereas Ad4-prM-E vaccination only induces a …

Regulators Of Oncogenic Mutant Tp53 Gain Of Function., Satomi Yamamoto, Tomoo Iwakuma

Manuscripts, Articles, Book Chapters and Other Papers

The tumor suppressor p53 (TP53) is the most frequently mutated human gene. Mutations in TP53 not only disrupt its tumor suppressor function, but also endow oncogenic gain-of-function (GOF) activities in a manner independent of wild-type TP53 (wtp53). Mutant TP53 (mutp53) GOF is mainly mediated by its binding with other tumor suppressive or oncogenic proteins. Increasing evidence indicates that stabilization of mutp53 is crucial for its GOF activity. However, little is known about factors that alter mutp53 stability and its oncogenic GOF activities. In this review article, we primarily summarize key regulators of mutp53 stability/activities, including genotoxic stress, post-translational modifications, ubiquitin …

Modeling Reveals The Dependence Of Hippocampal Neurogenesis Radiosensitivity On Age And Strain Of Rats, Eliedonna Cacao, Sidath Kapukotuwa, Francis A. Cucinotta

Health Physics and Diagnostic Sciences Faculty Research

Cognitive dysfunction following radiation treatment for brain cancers in both children and adults have been correlated to impairment of neurogenesis in the hippocampal dentate gyrus. Various species and strains of rodent models have been used to study radiation-induced changes in neurogenesis and these investigations have utilized only a limited number of doses, dose-fractions, age and time after exposures conditions. In this paper, we have extended our previous mathematical model of radiation-induced hippocampal neurogenesis impairment of C57BL/6 mice to delineate the time, age, and dose dependent alterations in neurogenesis of a diverse strain of rats. To the best of our knowledge, …

Retinopathy Of Prematurity: A Major Review And Situation Analysis In Egypt, Ihab S. Othman

Journal of Medicine in Scientific Research

Retinopathy of prematurity (ROP) remains a major cause of childhood blindness in developing countries. As childhood and neonatal mortality in Egypt has shown tremendous improvement over the past two decades, it is expected to encounter an increasing number of cases of blindness from ROP in surviving infants unless strict guidelines and cooperation between different involved departments are explicitly set. In this review article, the author highlights the studies conducted and published risk factors, recommends protocols for early diagnosis, and describes management strategies to lessen or prevent blindness related to ROP.

Psychological Respect For Patients With Breast Cancer Using Radial Incision Which Gives Better Cosmetic Outcome After Conservative Breast Surgery, Adel K. Barsoum, Hytham R. Yassin

Journal of Medicine in Scientific Research

Background Breast cancer is considered as one of the most common cancers affecting women, and remains one of the world's biggest killers. Once diagnosed as a breast cancer patient, a woman can be exposed to psychological trauma that is manifested as stress, anxiety, and even depression. Since surgery is the most important part of breast cancer management protocol, the first time a woman looks to her body after surgery can be harmful. Despite this gloomy picture, there have been some dramatic modifications recently in the treatment of breast cancer, especially in early detected tumors. One of them is the clear …

The Role Of Urinary Hepcidin In Early Detection Of Iron Deficiency Anemia, Aisha El Sheimy, Azza Omran, Fify Helmy, Hala I. Mouhamed, Sohaila Ali, Youssof Mohamed

Journal of Medicine in Scientific Research

Iron deficiency anemia (IDA) is one of the most severe and important nutritional deficiencies, especially in children all over the world. Iron deficiency may occur because of inadequate dietary intake, increase in physiological needs of the nutrient, and/or increased losses, which may lead to anemia. IDA has been associated with cognitive, motor, and behavioral impairment in children. The most commonly used tests to determine iron status include serum iron levels, ferritin, and others. However, these test have limited role in diagnosis of IDA. For this reason, there is great interest in investigating effective method for the diagnosis of IDA. The …

Anti-Acetylcholine Receptor Antibodies As A Diagnostic Marker For Myasthenia Gravis, Aisha El-Shimy, Hala I. Mohamed, Iman Kamel, Magdy Khalaf, Youssof Abd El Motamad

Journal of Medicine in Scientific Research

Background Myasthenia gravis (MG) is a common primary disorder of neuromuscular transmission, which is characterized by fluctuating weakness of a certain voluntary muscles, particularly those innervated by motor nuclei of the brain stem, that is, ocular and mastication muscles, and caused by antibodies binding to components in the neuromuscular junction. Most MG cases demonstrate elevated serum levels of acetylcholine receptor (ACh-R) antibodies, which cause partial or complete inhibition of receptor function and complement-mediated focal lysis of the postsynaptic membrane. ACh-R antibodies are detected in the serum of more than 80–90% patients with generalized MG, in ~50% with ocular myasthenia, and …

Results Of Compression Plating Versus Locked Intramedullary Nailing Fixation In The Treatment Of Humeral Shaft Fractures In Adults, Ahmad Shawakat Rizk, Hassan Hussein Ahmad Abdallah, Mohammed Gamal El Din Al Ashahab, Said Ibrahim Said Abdelmotalb

Journal of Medicine in Scientific Research

Background Most humerus shaft fractures can be treated successfully using the conservative methods. When choosing surgical fixation, there is a debate between the use of plate and screws and intramedullary nails. Aims The aim of this study was to compare the results of the dynamic compression plate and the antegrade interlocked humeral nail in the fixation of humerus shaft fractures. Patients and methods A total of 40 patients were selected by a randomized method to be treated by either method; there were 20 patients in each group and patients were followed up for at least 6 months until union. Result …

Als Mutations Of Fus Suppress Protein Translation And Disrupt The Regulation Of Nonsense-Mediated Decay, Marisa Kamelgarn, Jing Chen, Lisha Kuang, Huan Jin, Edward J. Kasarskis, Haining Zhu

Toxicology and Cancer Biology Faculty Publications

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease characterized by preferential motor neuron death. Approximately 15% of ALS cases are familial, and mutations in the fused in sarcoma (FUS) gene contribute to a subset of familial ALS cases. FUS is a multifunctional protein participating in many RNA metabolism pathways. ALS-linked mutations cause a liquid–liquid phase separation of FUS protein in vitro, inducing the formation of cytoplasmic granules and inclusions. However, it remains elusive what other proteins are sequestered into the inclusions and how such a process leads to neuronal dysfunction and degeneration. In this study, we developed …

Trypanosoma Brucei Prmt1 Is A Nucleic Acid Binding Protein With A Role In Energy Metabolism And The Starvation Stress Response., Lucie Kafková, Chengjian Tu, Kyle L. Pazzo, Kyle P. Smith, Erik W. Debler, Kimberly S. Paul, Jun Qu, Laurie K. Read

Department of Biochemistry and Molecular Biology Faculty Papers

In Trypanosoma brucei and related kinetoplastid parasites, transcription of protein coding genes is largely unregulated. Rather, mRNA binding proteins, which impact processes such as transcript stability and translation efficiency, are the predominant regulators of gene expression. Arginine methylation is a posttranslational modification that preferentially targets RNA binding proteins and is, therefore, likely to have a substantial impact on T. brucei biology. The data presented here demonstrate that cells depleted of T. brucei PRMT1 (TbPRMT1), a major type I protein arginine methyltransferase, exhibit decreased virulence in an animal model. To understand the basis of this phenotype, quantitative global proteomics was employed …