Description: Uniprot:P11021 Alternative Names： Specificity

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TA0729 GRP78 Antibody Order 021-34695924 [email protected] Support 400-6123-828 50ul [email protected] 100 uL √ √ Web www.ab-mart.com.cn Description: Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen. Involved in the correct folding of proteins and degradation of misfolded proteins via its interaction with DNAJC10/ERdj5, probably to facilitate the release of DNAJC10/ERdj5 from its substrate (By similarity). Acts as a key repressor of the ERN1/IRE1-mediated unfolded protein response (UPR). In the unstressed endoplasmic reticulum, recruited by DNAJB9/ERdj4 to the luminal region of ERN1/IRE1, leading to disrupt the dimerization of ERN1/IRE1, thereby inactivating ERN1/IRE1 (By similarity). Accumulation of misfolded protein in the endoplasmic reticulum causes release of HSPA5/BiP from ERN1/IRE1, allowing homodimerization and subsequent activation of ERN1/IRE1 (By similarity). Plays an auxiliary role in post-translational transport of small presecretory proteins across endoplasmic reticulum (ER). May function as an allosteric modulator for SEC61 channel-forming translocon complex, likely cooperating with SEC62 to enable the productive insertion of these precursors into SEC61 channel. Appears to specifically regulate translocation of precursors having inhibitory residues in their mature region that weaken channel gating. Uniprot:P11021 Alternative Names： 78 kDa glucose regulated protein; 78 kDa glucose-regulated protein; AL022860; AU019543; BIP; D2Wsu141e; D2Wsu17e; Endoplasmic reticulum lumenal Ca(2+)-binding protein grp78; Endoplasmic reticulum lumenal Ca2+ binding protein grp78; Epididymis secretory sperm binding protein Li 89n; FLJ26106; Glucose Regulated Protein 78kDa; GRP 78; GRP-78; GRP78; GRP78_HUMAN; Heat shock 70 kDa protein 5; Heat Shock 70kDa Protein 5; Heat shock protein family A (Hsp70) member 5; HEL S 89n; Hsce70; HSPA 5; HSPA5; Immunoglobulin Heavy Chain Binding Protein; Immunoglobulin heavy chain- binding protein; mBiP; MIF2; Sez7; Specificity: GRP78 Antibody detects endogenous levels of total GRP78. Reactivity:Human, Mouse, Rat, Monkey Source:Rabbit Mol.Wt.: 75kD; 72kDa(Calculated). Storage Condition: Store at -20 °C. Stable for 12 months from date of receipt. Application: WB 1:1000-1:2000；IHC/IF 1:50-1:500.

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FK506-Binding Protein 12.6/1B, a Negative Regulator of [Ca2+], Rescues Memory and Restores Genomic Regulation in the Hippocampus of Aging Rats

This Accepted Manuscript has not been copyedited and formatted. The final version may differ from this version. A link to any extended data will be provided when the final version is posted online. Research Articles: Neurobiology of Disease FK506-Binding Protein 12.6/1b, a negative regulator of [Ca2+], rescues memory and restores genomic regulation in the hippocampus of aging rats John C. Gant1, Eric M. Blalock1, Kuey-Chu Chen1, Inga Kadish2, Olivier Thibault1, Nada M. Porter1 and Philip W. Landfield1 1Department of Pharmacology & Nutritional Sciences, University of Kentucky, Lexington, KY 40536 2Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35294 DOI: 10.1523/JNEUROSCI.2234-17.2017 Received: 7 August 2017 Revised: 10 October 2017 Accepted: 24 November 2017 Published: 18 December 2017 Author contributions: J.C.G. and P.W.L. designed research; J.C.G., E.M.B., K.-c.C., and I.K. performed research; J.C.G., E.M.B., K.-c.C., I.K., and P.W.L. analyzed data; J.C.G., E.M.B., O.T., N.M.P., and P.W.L. wrote the paper. Conflict of Interest: The authors declare no competing financial interests. NIH grants AG004542, AG033649, AG052050, AG037868 and McAlpine Foundation for Neuroscience Research Corresponding author: Philip W. Landfield, [email protected], Department of Pharmacology & Nutritional Sciences, University of Kentucky, 800 Rose Street, UKMC MS 307, Lexington, KY 40536 Cite as: J. Neurosci ; 10.1523/JNEUROSCI.2234-17.2017 Alerts: Sign up at www.jneurosci.org/cgi/alerts to receive customized email alerts when the fully formatted version of this article is published.
Mutants in Three Novel Complementation Groups Inhibit

Mutants in Three Novel Complementation Groups Inhibit Membrane Protein Insertion into and Soluble Protein Translocation across the Endoplasmic Reticulum Membrane of Saccharomyces cerevisiae Neil Green,* Hong Fang, $ and Peter Walter* *Department ofBiochemistry and Biophysics, School ofMedicine, University of California, San Francisco, California 94143-0448; and tDepartment of Microbiology and Immunology, School ofMedicine, Vanderbilt University, Nashville, Tennessee 37232-2363 Abstract. We have isolated mutants that inhibit mem- tations in SEC61 and SEC63, which were previously brane protein insertion into the ER membrane of Sac- isolated as mutants inhibiting the translocation of solu- charomyces cerevisiae. The mutants were contained in ble proteins, also affect the insertion of membrane three complementation groups, which we have named proteins into the ER. Taken together our data indicate SEC70, SEC1, and SEC72. The mutants also inhib- that the process of protein translocation across the ER ited the translocation of soluble proteins into the lu- membrane involves a much larger number of gene men of the ER, indicating that they pleiotropically products than previously appreciated . Moreover, differ- affect protein transport across and insertion into the ent translocation substrates appear to have different re- ER membrane. Surprisingly, the mutants inhibited the quirements for components of the cellular targeting translocation and insertion of different proteins to dras- and translocation apparatus . tically different degrees. We have also shown that mu- SCENT genetic studies in Saccharomyces cerevisiae Interestingly, not all proteins passing through the secretory have shown that the SEC61, SEC62, and SEC63 pathway were equally affected by mutations in SEC61, SEC- genes are required for secretory protein translocation 62, and SEC63 ; the translocation of pre-invertase showed into the lumen of the ER (Deshaies and Schekman, 1987; little inhibition in mutant cells (Rothblatt et al., 1989) and Rothblatt et al., 1989).
Computational Genome-Wide Identification of Heat Shock Protein Genes in the Bovine Genome [Version 1; Peer Review: 2 Approved, 1 Approved with Reservations]

F1000Research 2018, 7:1504 Last updated: 08 AUG 2021 RESEARCH ARTICLE Computational genome-wide identification of heat shock protein genes in the bovine genome [version 1; peer review: 2 approved, 1 approved with reservations] Oyeyemi O. Ajayi1,2, Sunday O. Peters3, Marcos De Donato2,4, Sunday O. Sowande5, Fidalis D.N. Mujibi6, Olanrewaju B. Morenikeji2,7, Bolaji N. Thomas 8, Matthew A. Adeleke 9, Ikhide G. Imumorin2,10,11 1Department of Animal Breeding and Genetics, Federal University of Agriculture, Abeokuta, Nigeria 2International Programs, College of Agriculture and Life Sciences, Cornell University, Ithaca, NY, 14853, USA 3Department of Animal Science, Berry College, Mount Berry, GA, 30149, USA 4Departamento Regional de Bioingenierias, Tecnologico de Monterrey, Escuela de Ingenieria y Ciencias, Queretaro, Mexico 5Department of Animal Production and Health, Federal University of Agriculture, Abeokuta, Nigeria 6Usomi Limited, Nairobi, Kenya 7Department of Animal Production and Health, Federal University of Technology, Akure, Nigeria 8Department of Biomedical Sciences, Rochester Institute of Technology, Rochester, NY, 14623, USA 9School of Life Sciences, University of KwaZulu-Natal, Durban, 4000, South Africa 10School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, 30032, USA 11African Institute of Bioscience Research and Training, Ibadan, Nigeria v1 First published: 20 Sep 2018, 7:1504 Open Peer Review https://doi.org/10.12688/f1000research.16058.1 Latest published: 20 Sep 2018, 7:1504 https://doi.org/10.12688/f1000research.16058.1 Reviewer Status Invited Reviewers Abstract Background: Heat shock proteins (HSPs) are molecular chaperones 1 2 3 known to bind and sequester client proteins under stress. Methods: To identify and better understand some of these proteins, version 1 we carried out a computational genome-wide survey of the bovine 20 Sep 2018 report report report genome.
SEC62 Rabbit Polyclonal Antibody – TA319720 | Origene

OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for TA319720 SEC62 Rabbit Polyclonal Antibody Product data: Product Type: Primary Antibodies Applications: IF, IHC, WB Recommended Dilution: WB: 0.5 - 1 ug/mL, ICC: 5 ug/mL, IF: 20 ug/mL Reactivity: Human, Mouse, Rat Host: Rabbit Isotype: IgG Clonality: Polyclonal Immunogen: SEC62 antibody was raised against an 18 amino acid synthetic peptide near the carboxy terminus of human SEC62. Formulation: SEC62 Antibody is supplied in PBS containing 0.02% sodium azide. Concentration: 1ug/ul Purification: SEC62 Antibody is affinity chromatography purified via peptide column. Conjugation: Unconjugated Storage: Store at -20°C as received. Stability: Stable for 12 months from date of receipt. Gene Name: SEC62 homolog, preprotein translocation factor Database Link: NP_003253 Entrez Gene 69276 MouseEntrez Gene 294912 RatEntrez Gene 7095 Human Q99442 Background: SEC62 Antibody: SEC62 is an integral membrane protein located in the rough endoplasmic reticulum (ER) and is part of the SEC61-SEC62-SEC63 complex that is the central component of the protein translocation apparatus of the ER membrane. It is speculated that SEC61- SEC62-SEC63 may perform post-translational protein translocation into the ER and might also perform the backward transport of ER proteins that are subject to the ubiquitin-proteasome- dependent degradation pathway. Silencing of this gene with RNAi dramatically reduced the migration and invasive potential of numerous tumor cell lines, suggesting that it may be an attractive target for therapy of various tumors.
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus

Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated.
Sec62/Ki67 and P16/Ki67 Dual-Staining Immunocytochemistry

Archives of Gynecology and Obstetrics (2019) 299:825–833 https://doi.org/10.1007/s00404-018-5021-0 GYNECOLOGIC ONCOLOGY Sec62/Ki67 and p16/Ki67 dual‑staining immunocytochemistry in vulvar cytology for the identifcation of vulvar intraepithelial neoplasia and vulvar cancer: a pilot study Ferenc Zoltan Takacs1 · Julia Caroline Radosa1 · Florian Bochen2 · Ingolf Juhasz‑Böss1 · Erich‑Franz Solomayer1 · Rainer M. Bohle3 · Georg‑Peter Breitbach1 · Bernard Schick2 · Maximilian Linxweiler2 Received: 22 October 2018 / Accepted: 12 December 2018 / Published online: 4 January 2019 © Springer-Verlag GmbH Germany, part of Springer Nature 2019 Abstract Purpose The aim of this study was to analyze the diagnostic performance of a newly established immunocytochemical dual-staining protocol for the simultaneous expression of SEC62 and Ki67 in vulvar liquid-based cytology specimens for the identifcation of vulvar intraepithelial neoplasia (VIN) and vulvar cancer. In addition, we investigated the p16/Ki67 dual stain, which has already been established in cervical cytology. Materials and methods For this pilot study, residual material from liquid-based cytology was collected retrospectively from 45 women. The presence of one or more double-immunoreactive cells was considered as a positive test result for Sec62/Ki67 and p16/Ki67 dual staining. The test results were correlated with the course of histology. Results All cases of VIN and vulvar cancer were Sec62/Ki67 and p16/Ki67 dual-stain positive, and normal and low-grade squamous intraepithelial lesions were all negative. The sensitivity of cytology for VIN + cases was 100% (22/22), whereas punch biopsy classifed one case of vulvar carcinoma as infammation. All cases with high-intensity (grades 3 and 4) Sec62 staining in Sec62/Ki67-positive cases were carcinomas.
Rabbit Anti-SEC62/FITC Conjugated Antibody-SL19619R-FITC

SunLong Biotech Co.,LTD Tel: 0086-571- 56623320 Fax:0086-571- 56623318 E-mail:[email protected] www.sunlongbiotech.com Rabbit Anti-SEC62/FITC Conjugated antibody SL19619R-FITC Product Name: Anti-SEC62/FITC Chinese Name: FITC标记的TransporterSEC62抗体 Dtrp1; FLJ32803; hTP-1; HTP1; Membrane protein SEC62, S.cerevisiae, homolog of; Alias: OTTHUMP00000213390; sec62; SEC62 homolog (S. cerevisiae); SEC62_HUMAN; TLOC1; TP-1; Translocation protein 1; Translocation protein sec62. Organism Species: Rabbit Clonality: Polyclonal React Species: Human,Mouse,Rat,Dog,Pig,Cow,Horse,Rabbit,Sheep, ICC=1:50-200IF=1:50-200 Applications: not yet tested in other applications. optimal dilutions/concentrations should be determined by the end user. Molecular weight: 46kDa Form: Lyophilized or Liquid Concentration: 1mg/ml immunogen: KLH conjugated synthetic peptide derived from human SEC62 Lsotype: IgG Purification: affinity purified by Protein A Storage Buffer: 0.01Mwww.sunlongbiotech.com TBS(pH7.4) with 1% BSA, 0.03% Proclin300 and 50% Glycerol. Store at -20 °C for one year. Avoid repeated freeze/thaw cycles. The lyophilized antibody is stable at room temperature for at least one month and for greater than a year Storage: when kept at -20°C. When reconstituted in sterile pH 7.4 0.01M PBS or diluent of antibody the antibody is stable for at least two weeks at 2-4 °C. background: The Sec61 complex is the central component of the protein translocation apparatus of the endoplasmic reticulum (ER) membrane. The protein encoded by this gene and SEC63 protein are found to be associated with ribosome-free SEC61 complex. It is Product Detail: speculated that Sec61-Sec62-Sec63 may perform post-translational protein translocation into the ER.
A Clearer Picture of the ER Translocon Complex Max Gemmer and Friedrich Förster*

© 2020. Published by The Company of Biologists Ltd | Journal of Cell Science (2020) 133, jcs231340. doi:10.1242/jcs.231340 REVIEW A clearer picture of the ER translocon complex Max Gemmer and Friedrich Förster* ABSTRACT et al., 1986). SP-equivalent N-terminal transmembrane helices that The endoplasmic reticulum (ER) translocon complex is the main gate are not cleaved off can also target proteins to the ER through the into the secretory pathway, facilitating the translocation of nascent same mechanism. In this SRP-dependent co-translational ER- peptides into the ER lumen or their integration into the lipid membrane. targeting mode, ribosomes associate with the ER membrane via ER Protein biogenesis in the ER involves additional processes, many of translocon complexes. These membrane protein complexes them occurring co-translationally while the nascent protein resides at translocate nascent soluble proteins into the ER, integrate nascent the translocon complex, including recruitment of ER-targeted membrane proteins into the ER membrane, mediate protein folding ribosome–nascent-chain complexes, glycosylation, signal peptide and membrane protein topogenesis, and modify them chemically. In cleavage, membrane protein topogenesis and folding. To perform addition to co-translational protein import and translocation, distinct such varied functions on a broad range of substrates, the ER ER translocon complexes enable post-translational translocation and translocon complex has different accessory components that membrane integration. This post-translational pathway is widespread associate with it either stably or transiently. Here, we review recent in yeast (Panzner et al., 1995), whereas higher eukaryotes primarily structural and functional insights into this dynamically constituted use it for relatively short peptides (Schlenstedt and Zimmermann, central hub in the ER and its components.
Detection of Transient in Vivo Interactions Between Substrate And

Molecular Biology of the Cell Vol. 10, 329–344, February 1999 Detection of Transient In Vivo Interactions between Substrate and Transporter during Protein Translocation into the Endoplasmic Reticulum Martin Du¨ nnwald,* Alexander Varshavsky,† and Nils Johnsson*‡ *Max-Delbru¨ ck-Laboratorium, D-50829 Ko¨ln, Germany; and †Division of Biology, California Institute of Technology, Pasadena, California 91125 Submitted October 2, 1998; Accepted November 11, 1998 Monitoring Editor: Peter Walter The split-ubiquitin technique was used to detect transient protein interactions in living cells. Nub, the N-terminal half of ubiquitin (Ub), was fused to Sec62p, a component of the protein translocation machinery in the endoplasmic reticulum of Saccharomyces cerevisiae. Cub, the C-terminal half of Ub, was fused to the C terminus of a signal sequence. The reconstitution of a quasi-native Ub structure from the two halves of Ub, and the resulting cleavage by Ub-speciﬁc proteases at the C terminus of Cub, serve as a gauge of proximity between the two test proteins linked to Nub and Cub. Using this assay, we show that Sec62p is spatially close to the signal sequence of the prepro-a-factor in vivo. This proximity is conﬁned to the nascent polypeptide chain immediately following the signal sequence. In addition, the extent of proximity depends on the nature of the signal sequence. Cub fusions that bore the signal sequence of invertase resulted in a much lower Ub reconstitution with Nub-Sec62p than otherwise identical test proteins bearing the signal sequence of prepro-a-factor. An inactive derivative of Sec62p failed to interact with signal sequences in this assay.
Aneuploidy: Using Genetic Instability to Preserve a Haploid Genome?

Health Science Campus FINAL APPROVAL OF DISSERTATION Doctor of Philosophy in Biomedical Science (Cancer Biology) Aneuploidy: Using genetic instability to preserve a haploid genome? Submitted by: Ramona Ramdath In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomedical Science Examination Committee Signature/Date Major Advisor: David Allison, M.D., Ph.D. Academic James Trempe, Ph.D. Advisory Committee: David Giovanucci, Ph.D. Randall Ruch, Ph.D. Ronald Mellgren, Ph.D. Senior Associate Dean College of Graduate Studies Michael S. Bisesi, Ph.D. Date of Defense: April 10, 2009 Aneuploidy: Using genetic instability to preserve a haploid genome? Ramona Ramdath University of Toledo, Health Science Campus 2009 Dedication I dedicate this dissertation to my grandfather who died of lung cancer two years ago, but who always instilled in us the value and importance of education. And to my mom and sister, both of whom have been pillars of support and stimulating conversations. To my sister, Rehanna, especially- I hope this inspires you to achieve all that you want to in life, academically and otherwise. ii Acknowledgements As we go through these academic journeys, there are so many along the way that make an impact not only on our work, but on our lives as well, and I would like to say a heartfelt thank you to all of those people: My Committee members- Dr. James Trempe, Dr. David Giovanucchi, Dr. Ronald Mellgren and Dr. Randall Ruch for their guidance, suggestions, support and confidence in me. My major advisor- Dr. David Allison, for his constructive criticism and positive reinforcement.
Genomic Identification, Evolution and Sequence Analysis of the Heat

G C A T T A C G G C A T genes Article Genomic Identification, Evolution and Sequence Analysis of the Heat-Shock Protein Gene Family in Buffalo 1, 2, 3 4 1 Saif ur Rehman y, Asif Nadeem y , Maryam Javed , Faiz-ul Hassan , Xier Luo , Ruqayya Bint Khalid 3 and Qingyou Liu 1,* 1 State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning 530005, China; [email protected] (S.u.R.); [email protected] (X.L.) 2 Department of Biotechnology, Virtual University of Pakistan, Lahore-54000, Pakistan; [email protected] 3 Institute of Biochemistry and Biotechnology, University of Veterinary and Animal Sciences, Lahore-54000, Pakistan; [email protected] (M.J.); [email protected] (R.B.K.) 4 Institute of Animal and Dairy Sciences, Faculty of Animal Husbandry, University of Agriculture, Faisalabad-38040, Pakistan; [email protected] * Correspondence: [email protected]; Tel.: +86-138-7880-5296 These authors contributed equally to this manuscript. y Received: 26 October 2020; Accepted: 18 November 2020; Published: 23 November 2020 Abstract: Heat-shock proteins (HSP) are conserved chaperones crucial for protein degradation, maturation, and refolding. These adenosine triphosphate dependent chaperones were classified based on their molecular mass that ranges between 10–100 kDA, including; HSP10, HSP40, HSP70, HSP90, HSPB1, HSPD, and HSPH1 family. HSPs are essential for cellular responses and imperative for protein homeostasis and survival under stress conditions. This study performed a computational analysis of the HSP protein family to better understand these proteins at the molecular level.
Identification of Cyclin B1 and Sec62 As Biomarkers for Recurrence In

Weng et al. Molecular Cancer 2012, 11:39 http://www.molecular-cancer.com/content/11/1/39 RESEARCH Open Access Identification of cyclin B1 and Sec62 as biomarkers for recurrence in patients with HBV-related hepatocellular carcinoma after surgical resection Li Weng1†, Juan Du1†, Qinghui Zhou1, Binbin Cheng1, Jun Li1, Denghai Zhang2 and Changquan Ling1,3* Abstract Background: Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Frequent tumor recurrence after surgery is related to its poor prognosis. Although gene expression signatures have been associated with outcome, the molecular basis of HCC recurrence is not fully understood, and there is no method to predict recurrence using peripheral blood mononuclear cells (PBMCs), which can be easily obtained for recurrence prediction in the clinical setting. Methods: According to the microarray analysis results, we constructed a co-expression network using the k-core algorithm to determine which genes play pivotal roles in therecurrenceofHCCassociatedwiththehepatitisBvirus (HBV) infection. Furthermore, we evaluated the mRNA and protein expressions in the PBMCs from 80 patients with or without recurrence and 30 healthy subjects. The stability of the signatures was determined in HCC tissues from the same 80 patients. Data analysis included ROC analysis, correlation analysis, log-lank tests, and Cox modeling to identify independent predictors of tumor recurrence. Results: The tumor-associated proteins cyclin B1, Sec62, and Birc3 were highly expressed in a subset of samples of recurrent HCC; cyclin B1, Sec62, and Birc3 positivity was observed in 80%, 65.7%, and 54.2% of the samples, respectively. The Kaplan-Meier analysis revealed that high expression levels of these proteins was associated with significantly reduced recurrence-free survival.