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Miranda da Costa, Natacha Malu, Caio Tadashi Saab Abe, Geovanni Pereira Mitre, Ricardo Alves Mesquita, Maria Sueli da Silva Kataoka, André Luis Ribeiro Ribeiro, Ruy Gastaldoni Jaeger, Sérgio de Melo Alves-Júnior, Andrew Mark Smith, and João de Jesus Viana Pinheiro. "HIF-1α is Overexpressed in Odontogenic Keratocyst Suggesting Activation of HIF-1α and NOTCH1 Signaling Pathways." Cells 8, no. 7 (July 17, 2019): 731. http://dx.doi.org/10.3390/cells8070731.
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Background: The odontogenic keratocyst (OKC) is an odontogenic cyst that shows aggressive and intriguing biological behavior. It is suggested that a hypoxic environment occurs in OKC, which led us to investigate the immunoexpression and location of hypoxia-inducible factor 1-alpha (HIF-1α) and other hypoxia-related proteins. Methods: Twenty cases of OKC were evaluated for the expression of Notch homolog 1 (NOTCH1), HIF-1α, disintegrin and metalloproteinase domain-containing protein 12 (ADAM-12), and heparin-binding epidermal growth factor-like growth factor (HBEGF) by immunohistochemistry and compared to eight control cases of calcifying odontogenic cystic (COC), orthokeratinized odontogenic cyst (OOC), and normal oral mucosa (OM) in basal and parabasal layers. Results: In OKC, all the proteins tested were expressed significantly higher in both basal (except for NOTCH1 and HBEGF in OOC) and suprabasal epithelial layers compared to controls. Looking at the epithelial layers within OKC, we observed an increased NOTCH1 and HIF-1α expression in parabasal layers. Conclusions: These results suggest that hypoxia occurs more intensively in OKC compared to COC, OM, and OOC. Hypoxia appeared to be stronger in parabasal layers as observed by higher HIF-1α expression in upper cells. Overexpression of NOTCH1, ADAM-12, and HBEGF in OKC was observed, which suggests that microenvironmental hypoxia could potentially regulate the expression of hypoxia-related proteins, and consequently, its clinical and biological behavior.
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Swain, Niharika, LS Poonja, and Kamlesh Dekate. "Orthokeratinized Odontogenic Cyst." Journal of Contemporary Dentistry 2, no. 2 (2012): 31–33. http://dx.doi.org/10.5005/jp-journals-10031-1006.
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ABSTRACT Orthokeratinized odontogenic cyst (OOC) is a developmental cyst of odontogenic origin and was initially defined as the uncommon orthokeratinized variant of odontogenic keratocyst (OKC). However, recently World Health Organization has designated OOC as a distinct clinicopathologic entity as it has peculiar clinicopathologic aspects when compared to other developmental odontogenic cysts, especially OKCs. The orthokeratinized odontogenic cyst is histologically characterized by a thin, uniform, epithelial lining with orthokeratinization and a subjacent prominent granular cell layer. The purpose of the article is to present a case of OOC arising in the anterior mandible, an unusual site for the lesion and also highlights the importance of distinguishing it from the more commonly occurring keratocystic odontogenic tumor (KCOT). How to cite this article Swain N, Patel S, Poonja LS, Pathak J, Dekate K. Orthokeratinized Odontogenic Cyst. J Contemp Dent 2012;2(2):31-33.
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Freda, Pamela, Maria Fleseriu, Akexander V. Dreval, Yulia Pokramovich, Irina Bondar, Elena Isaeva, Wenyu Huang, et al. "Safety Results From MPOWERED, a Phase 3 Trial of Oral Octreotide Capsules in Adults With Acromegaly." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A527—A528. http://dx.doi.org/10.1210/jendso/bvab048.1074.
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Abstract Background: Injectable somatostatin receptor ligands (iSRLs) have been a mainstay in acromegaly treatment. Oral octreotide capsules (OOC; MYCAPSSA®) were recently approved in the United States. Results from the placebo-controlled CHIASMA OPTIMAL and open-label CH-ACM-01 studies showed an OOC safety profile consistent with that of iSRLs with no new or unexpected safety signals. Results of the MPOWERED trial have enabled a comparison of OOC safety and efficacy with iSRLs. Methods: To enter MPOWERED, patients must have the following: acromegaly diagnosis, biochemical control of acromegaly (insulin-like growth factor I <1.3 × upper limit of normal; mean integrated growth hormone <2.5 ng/mL), and ≥6 months’ iSRLs treatment (octreotide or lanreotide). Eligible patients entered a 26-week Run-in phase to determine the effective OOC dose; responders at week 24 then entered a 36-week randomized controlled treatment (RCT) phase receiving OOC or iSRLs. Safety was monitored as adverse events (AEs) in both arms throughout the trial, including the RCT. Results: In the RCT, incidence of treatment-emergent adverse events (TEAEs) was similar between groups; 39 patients (70.9%) in the OOC group and 26 (70.3%) in the iSRL group had ≥1 TEAE. 19 patients (34.5%) in the OOC and 15 (40.5%) in the iSRL group had treatment-related TEAEs. Occurrence was similar for serious AEs (OOC, 5.5%; iSRL, 8.1%) as well as TEAEs classified as severe (OOC, 9.1%; iSRL, 10.8%). One patient in the OOC group discontinued due to a TEAE. The most common gastrointestinal TEAEs were flatulence (OOC, 25.5%; iSRL, 21.6%), nausea (OOC, 20.0%; iSRL, 8.1%), diarrhea (OOC, 10.9%; iSRL, 13.5%), abdominal pain (OOC, 9.1%; iSRL, 8.1%), and constipation (OOC, 5.5%; iSRL, 13.5%). AEs of interest were infrequent, including cholelithiasis (OOC, n=0; iSRL, n=1 [2.7%]) and secondary hypothyroidism (OOC, n=1 [1.8%]; iSRL, n=0). In the iSRL group, 32.4% of patients reported injection site reactions (ISRs) during the RCT, and 47% of patients reported ISRs as part of the Acromegaly Treatment Satisfaction Questionnaire, a newly validated patient-reported outcome tool.1 Conclusion: Safety results from MPOWERED align with prior trials, showing that the OOC safety profile is consistent with that of iSRLs as well as the acromegaly disease burden. No new or unexpected safety signals were identified during the trial. Safety results were mostly similar between OOC and iSRLs, although patients in the OOC group did not experience any ISRs. 1Fleseriu M, et al. Pituitary. 2020 Aug;23(4):347-358.
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Gombos, Réka, and Ferenc Joó. "Selective hydrogenation of cinnamaldehyde and phospholipids in aqueous-organic biphasic systems with ruthenium(II) complex catalysts." Green Processing and Synthesis 3, no. 2 (April 1, 2014): 127–32. http://dx.doi.org/10.1515/gps-2014-0003.
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Abstract The new water-soluble complex [RuH(OOc)(mtppms)3] (OOc=octanoate, mtppms=monosulfonated triphenylphosphine) was synthesized and – together with the known [RuH(OAc)(mtppms)3] (OAc=acetate) – applied for aqueous-organic biphasic hydrogenation of cinnamaldehyde as well as for hydrogenation of soybean liposomes under mild conditions. The complexes showed pronounced selectivity (up to 75%) towards the hydrogenation of the C=O function in the α,β-unsaturated aldehyde; the selectivity was influenced by the pH of the aqueous phase and the hydrogen pressure. The C=C double bonds in soybean lecithin were only slowly reduced, however, at 5 bar H2 pressure the reaction rate was sufficient to achieve substantial conversion (approximately 20% of all double bonds) in the unsaturated fatty acids.
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Wegener, Maximilian D., Ralph P. Brooks, Suzanne Speers, Deborah Gosselin, and Merceditas Villanueva. "957. Efficacy of Using Disease Intervention Specialists (DIS) to Re-engage Out of Care HIV/HCV Co-Infected Persons into HCV Treatment." Open Forum Infectious Diseases 7, Supplement_1 (October 1, 2020): S509—S510. http://dx.doi.org/10.1093/ofid/ofaa439.1143.
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Abstract Background Published treatment cascades for HIV/HCV co-infection show WHO goals for HCV micro-elimination are not being met. Barriers include entry to care, access to DAA, treatment adherence, and out of care (OOC) patients. A Data to Care approach used to define persons with HIV (PWH) who are OOC, together with DPH-employed DIS to promote re-engagement has been successful for re-engaging OOC PWH. We modified this approach to re-engage OOC HIV/HCV coinfected persons. Methods Surveillance databases used: CTEDSS (CT Electronic Disease Surveillance System used for HCV) and eHARS (electronic HIV/AIDS Reporting System). Two OOC cohorts studied: HIV OOC for 12 months (no HIV lab 10/2018-10/2019) and 18 months (no HIV lab 12/2017-6/2019). Lists generated for the 2 cohorts matched to CTEDSS to determine the coinfected OOC. DIS supervisor performed pre-work/case conferencing on lists to assess DIS intervention eligibility. DIS success was defined as those who reengaged (made/kept appointment) out of those successfully contacted. Analysis: tests of homogeneity performed between those OOC and not OOC; evaluation of cases at each level of the intervention; measures of dispersion/central tendency performed illustrating reengagement workload. Project Flow Chart Results 12-month OOC: Non-baby boomers (p-value 0.05) and those with detectable HIV VLs (0.04) were more likely to be OOC; 53.7% were DIS-eligible; DIS initiation to client contact, 7 days average (range 4-11); 75 calls and 31 field visits for those successfully contacted; reengagement success rate, 39%. 18-month OOC: Non-baby boomers (0.017), Hispanic and Black race/ethnicity (0.043), and those with detectable HIV viral loads (0.002) were more likely to be OOC; 44% were DIS-eligible; DIS initiation to client contact, 12 days average (range 8-18); 74 calls and 36 field visits for those successfully contacted; reengagement success rate, 43%. Results for the Two Cohorts Out of Care and Workload Results Conclusion A data-to-care approach successfully identified, characterized, connected OOC HIV/HCV coinfected patients. DIS provided patient education, facilitating reengagement to care. DIS Success rates are encouraging but small; efforts were labor intensive. Additional strategies focused on preventing non-baby boomers, persons of color, and those with detectable HIV VLs from becoming OOC should be studied. Disclosures All Authors: No reported disclosures
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Basham, Stephen E., and Lesilee S. Rose. "The Caenorhabditis elegans polarity gene ooc-5 encodes a Torsin-related protein of the AAA ATPase superfamily." Development 128, no. 22 (November 15, 2001): 4645–56. http://dx.doi.org/10.1242/dev.128.22.4645.
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The PAR proteins are required for polarity and asymmetric localization of cell fate determinants in C. elegans embryos. In addition, several of the PAR proteins are conserved and localized asymmetrically in polarized cells in Drosophila, Xenopus and mammals. We have previously shown that ooc-5 and ooc-3 mutations result in defects in spindle orientation and polarity in early C. elegans embryos. In particular, mutations in these genes affect the re-establishment of PAR protein asymmetry in the P1 cell of two-cell embryos. We now report that ooc-5 encodes a putative ATPase of the Clp/Hsp100 and AAA superfamilies of proteins, with highest sequence similarity to Torsin proteins; the gene for human Torsin A is mutated in individuals with early-onset torsion dystonia, a neuromuscular disease. Although Clp/Hsp100 and AAA family proteins have roles in diverse cellular activities, many are involved in the assembly or disassembly of proteins or protein complexes; thus, OOC-5 may function as a chaperone. OOC-5 protein co-localizes with a marker of the endoplasmic reticulum in all blastomeres of the early C. elegans embryo, in a pattern indistinguishable from that of OOC-3 protein. Furthermore, OOC-5 localization depends on the normal function of the ooc-3 gene. These results suggest that OOC-3 and OOC-5 function in the secretion of proteins required for the localization of PAR proteins in the P1 cell, and may have implications for the study of torsion dystonia.
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Fleseriu, Maria, Alexander V. Dreval, Yulia Pokramovich, Irina Bondar, Elena Isaeva, Mark E. Molitch, Djuro P. Macut, et al. "A Phase 3 Large International Noninferiority Trial (MPOWERED): Assessing Maintenance of Response to Oral Octreotide Capsules in Comparison to Injectable Somatostatin Receptor Ligands." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A517. http://dx.doi.org/10.1210/jendso/bvab048.1056.
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Abstract Background: MPOWERED, a large phase 3 trial, assessed maintenance of response to oral octreotide capsules (OOC; MYCAPSSA®) compared to injectable somatostatin receptor ligands (iSRLs) in patients with acromegaly who responded to OOC and iSRLs (octreotide or lanreotide). OOC were recently approved in the US for patients with acromegaly who responded to and tolerated iSRLs. Methods: Eligibility criteria included age 18-75 years at screening, acromegaly diagnosis, disease evidence, biochemical control (insulin-like growth factor I [IGF-I] <1.3 × upper limit of normal [ULN] and mean integrated growth hormone [GH] <2.5 ng/mL) at screening, and ≥6 months’ iSRL treatment. Effective OOC dose was determined in a 26-week Run-in phase. Eligible patients (IGF-I <1.3 × ULN and mean integrated GH <2.5 ng/mL, week 24) were randomized to a 36-week controlled treatment phase (RCT), receiving OOC or iSRLs starting at week 26. The primary end point was a noninferiority assessment of proportion of patients biochemically controlled in the RCT (IGF-I <1.3 × ULN using time-weighted average). Other end points included nonresponse imputation of the primary end point, landmark analysis using proportion of responders based on average of last 2 IGF-I values at end of RCT, and change from baseline RCT (week 26) IGF-I and GH levels. Results: Of 146 enrolled patients, 92 entered the RCT (OOC, n=55; iSRLs, n=37). Both arms were well balanced for age, sex, and acromegaly duration. OOC demonstrated noninferiority to iSRLs in maintaining biochemical response, with 91% (CI, 80%-97%) of OOC and 100% (CI, 91%-100%) of iSRL groups maintaining control during the RCT. Of those responding at end of Run-in, 96% of patients on OOC maintained response during RCT. Using nonresponse imputation, 89% of OOC and 95% of iSRL groups were biochemically controlled in RCT. Landmark analysis of those respnding at end of Run-in showed that 94% of patients in each group maintained response at RCT end. In both groups, IGF-I levels were stable in the RCT, average IGF-I at baseline and RCT end being 0.9 × ULN (OOC) and 0.8 × ULN (iSRL). Mean change in GH from RCT start to RCT end was -0.03 ng/mL (OOC) and +0.29 ng/mL (iSRL). Safety data were mostly similar between groups; the OOC group did not experience injection site reactions. Conclusion: In this noninferiority trial in patients with acromegaly, OOC demonstrated maintenance of biochemical response compared to iSRLs. Results support the efficacy of OOC as a possible iSRL alternative.
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Flemig, Holger, Ingo Pantenburg, and Gerd Meyer. "Two 3-aminobenzoates of praseodymium, Pr(OOC-Ph-NH2)3(H2O) and Pr(OOC-Ph-NH2)(OOC-Ph-NH)." Journal of Alloys and Compounds 451, no. 1-2 (February 2008): 429–32. http://dx.doi.org/10.1016/j.jallcom.2007.04.230.
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Gordon, Murray B., Maria Fleseriu, Akexander V. Dreval, Yulia Pokramovich, Irina Bondar, Elena Isaeva, Mark E. Molitch, et al. "Improved Acromegaly Patient Satisfaction With Oral Octreotide Capsules Compared With Injectable Somatostatin Receptor Ligands in the MPOWERED Trial." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A520—A521. http://dx.doi.org/10.1210/jendso/bvab048.1062.
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Abstract Background: Improved patient-reported outcomes (PROs) are increasingly becoming a key treatment objective in acromegaly. Validated PROs were used to assess disease and treatment burden in the MPOWERED phase 3 trial in acromegaly, which also assessed safety and efficacy of oral octreotide capsules (OOC; MYCAPSSA®) compared to injectable SRLs (iSRLs). Methods: Eligible patients had acromegaly diagnosis, biochemical control of acromegaly (insulin-like growth factor I <1.3 × upper limit of normal; mean integrated growth hormone, <2.5 ng/mL) and ≥6 months’ iSRL treatment (octreotide or lanreotide). Eligible patients entered a 26-week Run-in phase to determine the effective OOC dose; responders at week 24 then entered a 36-week randomized controlled treatment (RCT) phase receiving OOC or iSRLs in a 3:2 ratio. The Acromegaly Treatment Satisfaction Questionnaire (Acro-TSQ) is a recently validated tool that includes 27 items in 6 domain scores for PROs in acromegaly.1 Acro-TSQ data were collected at baseline (reflecting outcomes on iSRLs), end of Run-in (reflecting outcomes on OOC), and end of RCT (OOC or iSRLs). Results: Of 146 enrolled patients, 92 entered RCT (OOC, N=55; iSRLs, N=37). Acro-TSQ scores at the end of Run-in (26 weeks’ OOC treatment) were compared to baseline (iSRLs). In the 92 patients randomized, 3 of 5 Acro-TSQ domains (emotional reaction, treatment convenience, and treatment satisfaction) showed significant improvement at end of Run-in compared to baseline. Injection site interference was not assessed as no injection site reactions were observed with OOC. Other domains showed a nonstatistically significant pattern of improvement at end of Run-in when compared to baseline. Patients randomized to iSRLs in the RCT after receiving OOC in the Run-in (N=37) reported more anxiety (RCT end, 53%; Run-in end, 29%) and frustration (RCT end, 45%; Run-in end, 34%) with iSRLs compared to OOC. Overall treatment satisfaction was higher while receiving OOC (Run-in end, 92%; after receiving iSRLs in RCT, 75%). Breakthrough symptoms were reported more frequently with iSRLs (31%) than OOC (15%) at the end of RCT. Conclusion: Higher patient satisfaction, convenience and emotional well-being, and improved symptom control based on the newly validated Acro-TSQ PRO reporting tool were observed with OOC compared to iSRLs in patients enrolled in the MPOWERED trial. 1Fleseriu M, et al. Pituitary. 2020 Aug;23(4):347-358.
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Li, X. B., H. B. Huang, and L. C. Wang. "Discussion on Construction of OCDMA PON Address Code-(F,K,2) Optical Orthogonal Codes." Advanced Materials Research 216 (March 2011): 804–8. http://dx.doi.org/10.4028/www.scientific.net/amr.216.804.
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Optical code division multiple access (OCDMA) passive optical network (PON) can find wide applications in the next optical access network. One of its key techniques of is construction of address code. Aiming at the facts that(F,K,1) optical orthogonal code (OOC) possesses good performance but capacity is small, and number of users in OCDMA PON is not very big thereafter OOC auto-correlation or cross-correlation may not be very strict,(F,K,2) OOC can be used as address codes for OCDMA PON. In this paper, the method of constructingOOC based on block design is discussed. The algorithm of construction (F,K,2) of OOC from block design is presented and simulated; several groups of(F,K,2) OOC are gained. The results show that the algorithm has good astringency and simplicity. It can construct(F,K,2) OOC effectively. It is feasible.
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Lucas Guimarães, Ana Maria, Patrícia Vitor De Souza, Ana Carolina Uchoa Vasconcelos, Sandra Beatriz Chaves Tarquinio, Adriana Etges, Ana Paula Neutzling Gomes, and Isadora Luana Flores. "Orthokeratinized Odontogenic Cyst (OOC): Report of Two Cases of OOC in Jaws." Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology 126, no. 3 (September 2018): e65. http://dx.doi.org/10.1016/j.oooo.2018.02.155.
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Hwang, Seong-Hye, Sangchul Lee, Jee Yoon Park, Jessie Sungyun Jeon, Young-Jae Cho, and Sejoong Kim. "Potential of Drug Efficacy Evaluation in Lung and Kidney Cancer Models Using Organ-on-a-Chip Technology." Micromachines 12, no. 2 (February 21, 2021): 215. http://dx.doi.org/10.3390/mi12020215.
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Organ-on-a-chip (OoC) is an exponential technology with the potential to revolutionize disease, toxicology research, and drug discovery. Recent advances in OoC could be utilized for drug screening in disease models to evaluate the efficacy of new therapies and support new tools for the understanding of disease mechanisms. Rigorous validation of this technology is required to determine whether OoC models may represent human-relevant physiology and predict clinical outcomes in target disease models. Achievements in the OoC field could reveal exciting new avenues for drug development and discovery. This review attempts to highlight the benefits of OoC as per our understanding of the cellular and molecular pathways in lung and kidney cancer models, and discusses the challenges in evaluating drug efficacy.
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Kaarj and Yoon. "Methods of Delivering Mechanical Stimuli to Organ-on-a-Chip." Micromachines 10, no. 10 (October 14, 2019): 700. http://dx.doi.org/10.3390/mi10100700.
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Recent advances in integrating microengineering and tissue engineering have enabled the creation of promising microengineered physiological models, known as organ-on-a-chip (OOC), for experimental medicine and pharmaceutical research. OOCs have been used to recapitulate the physiologically critical features of specific human tissues and organs and their interactions. Application of chemical and mechanical stimuli is critical for tissue development and behavior, and they were also applied to OOC systems. Mechanical stimuli applied to tissues and organs are quite complex in vivo, which have not adequately recapitulated in OOCs. Due to the recent advancement of microengineering, more complicated and physiologically relevant mechanical stimuli are being introduced to OOC systems, and this is the right time to assess the published literature on this topic, especially focusing on the technical details of device design and equipment used. We first discuss the different types of mechanical stimuli applied to OOC systems: shear flow, compression, and stretch/strain. This is followed by the examples of mechanical stimuli-incorporated OOC systems. Finally, we discuss the potential OOC systems where various types of mechanical stimuli can be applied to a single OOC device, as a better, physiologically relevant recapitulation model, towards studying and evaluating experimental medicine, human disease modeling, drug development, and toxicology.
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Severin, Kay, Ralph Bergs, Michael Maurus, Sharam Mihan, and Wolfgang Beck. "Metallkomplexe mit biologisch wichtigen Liganden, LXXV. Synthese metallorganischer Cobalt(III)-, Iridium(III)- und Ruthenium(II)-Komplexe mit α-Iminocarboxylat-Liganden Metal Complexes of Biologically Important Ligands, LXXV. Synthesis of Organometallic Cobalt(III), Iridium(III) and Ruthenium(II) Complexes with α-Iminocarboxylate Ligands." Zeitschrift für Naturforschung B 50, no. 2 (February 1, 1995): 265–74. http://dx.doi.org/10.1515/znb-1995-0220.
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The α-iminocarboxylato chelate complexes RuH(CO)[OOC-C(R1)=N-R2](PPh3)2 (1), η6-p-cymene)RuCl[OOC-C(R)=N-CH2CO2Me] (3) and Cp*CoI[OOC-C(R1)= N-R2] (4) have been obtained from RuHCl(CO)(PPh3)3, [(η6-p-cymene)RuCl2] and Cp*Co(CO)I2, respectively and 2-oxocarboxylate/amine. The structure of (η6-p-cymene)RuCl[OOC-C(CH3)= N-CH2CO2Me] (3a) has been determined by X-ray diffraction. By use of diamines the corresponding dinuclear cobalt and iridium complexes (5, 6) are formed from 2-oxocarboxylate and Cp*Co(CO)I2 or [Cp*IrCl2]2.
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Biermasz, Nienke, Maria Fleseriu, Akexander V. Dreval, Yulia Pokramovich, Irina Bondar, Elena Isaeva, Mark E. Molitch, et al. "Oral Octreotide Capsules Lowered Incidence and Improved Severity of Acromegaly Symptoms Compared to Injectable Somatostatin Receptor Ligands—Results From the MPOWERED Trial." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A522—A523. http://dx.doi.org/10.1210/jendso/bvab048.1065.
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Abstract Background: Patients with acromegaly may have high symptom burden. The phase 3 MPOWERED trial assessed control of acromegaly by oral octreotide capsules (OOC; MYCAPSSA®) in comparison to injectable somatostatin receptor ligands (iSRLs) in patients responding to both OOC and iSRLs. iSRLs have been first-line medical treatment for patients with acromegaly for decades. OOC are newly approved in the US for patients previously controlled on iSRLs. Methods: Eligibility criteria for MPOWERED included acromegaly diagnosis, biochemical control of acromegaly (insulin-like growth factor I <1.3 × upper limit of normal; mean integrated growth hormone, <2.5 ng/mL) and ≥6 months’ iSRL (octreotide, lanreotide) treatment. Eligible patients entered a 26-week Run-in phase to determine the effective OOC dose; responders at week 24 then entered a 36-week randomized controlled treatment (RCT) phase receiving OOC or iSRLs. Acromegaly symptom number and severity (mild to severe, 1-3) were collected. Total score was calculated by summating all severity scores (Acromegaly Index of Severity [AIS]). Symptom results were assessed using total AIS score and proportion of patients experiencing individual symptoms. Results: At beginning of Run-in, average AIS score of 92 randomized patients was 4.52, representative of symptoms experienced while previously receiving iSRLs. After 26 weeks’ OOC treatment at end of Run-in, average AIS score was significantly reduced to 3.46 (P<0.001). More than 80% of patients on OOC improved or maintained AIS score during Run-in compared to baseline. Over this 26-week period, there was a significant reduction in extremity swelling (P=0.01) and fatigue (P=0.03). During the RCT, of patients randomized to OOC (n=55), 73% maintained or improved AIS score, and 75% maintained or reduced overall number of active symptoms. In comparison, 68% of those randomized to iSRLs (n=37) maintained or improved AIS score, and 70% maintained or reduced overall number of active symptoms. Conclusion: Results from MPOWERED show that patients receiving OOC had significant improvement in number and severity of acromegaly symptoms after switching from iSRLs. These findings validate previous results from a phase 3 study of OOC in acromegaly in which patients switching to OOC from iSRLs showed significant reduction in joint pain, extremity swelling, and fatigue.1 1Melmed S, et al. JCEM. 2015;100(4):1699-1708.
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Samson, Susan Leanne, Lisa B. Nachtigall, Maria Fleseriu, Mark E. Molitch, Andrea Giustina, William Henry Ludlam, Gary Patou, et al. "One-Year Outcomes of the Open-Label Extension of CHIASMA OPTIMAL, a Phase 3 Study of Oral Octreotide Capsules in Acromegaly." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A515—A516. http://dx.doi.org/10.1210/jendso/bvab048.1054.
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Abstract Background: Based on the CHIASMA OPTIMAL study, oral octreotide capsules (OOC) were recently approved in the US as a long-term maintenance therapy for patients with acromegaly previously responding to injectable octreotide or lanreotide, somatostatin receptor ligands (SRLs). Results on longer-term efficacy and safety of OOC from the first 48 weeks of the open-label extension (OLE) of this study are presented here. Methods: Eligible patients had the option to enroll in the OLE of CHIASMA OPTIMAL following the double-blind placebo-controlled (DPC) period; 90% of patients who received OOC in the DPC period enrolled. All patients entering the OLE were initiated on a 60 mg/day dose of OOC and titrated up or down based on insulin-like growth factor I (IGF-I) level and/or acromegaly signs or symptoms. End points in the OLE were exploratory and included the proportion of patients who completed week 48 of the OLE, the proportion who completed as responders (defined as average IGF-I ≤1.0 × upper limit of normal [ULN] at weeks 46/48), and changes in IGF-I from baseline of DPC and OLE until week 48 of the OLE; multiple imputation (MI) was used for missing data. Results: Forty patients entered the OLE (n=20 each; OOC and placebo). Median exposure to OOC in the OLE was > 1 year for those who had been on placebo in the DPC and ≤ 21 months for those who had been on OOC. Dosing of OOC at the end of their participation in the OLE was 40 mg, n=3; 60 mg, n=10; and 80 mg, n=27. In those who received OOC during the DPC, 90% (n=18) completed 48 weeks of the OLE. Of responders at the end of the DPC period (n=14), 92.6% maintained response at OLE week 48. In patients from the OOC group who completed the DPC on study drug, average IGF-I using MI was 0.91 and 0.90 × ULN at OLE baseline and week 48, respectively. The mean change in IGF-I from the baseline of the DPC to OLE week 48 was 0.06 × ULN in patients who completed the DPC on OOC (n=19). In those who received placebo during the DPC, 70% (n=14) completed 48 weeks of the OLE. Of responders at the end of the DPC (n=5), 100% maintained response at OLE week 48. In patients from the placebo group who completed the DPC and did not revert to prior injectable therapy (n=9), the average IGF-I values were 1.09 and 0.87 × ULN at OLE baseline and week 48 respectively, using MI. The mean change in IGF-I from the baseline of the DPC to OLE week 48 was 0.08 × ULN in patients who completed the DPC on placebo (n=9). The most common treatment-emergent adverse events (TEAEs) were gastrointestinal; most were mild or moderate. The incidence of TEAEs was similar between patients who were on OOC or placebo during the DPC. The safety profile during the OLE did not show new concerns with increased duration of drug exposure. Conclusion: Long term maintenance of biochemical response to OOC is durable as assessed following ≤ 21 months of treatment. The OOC safety profile in the extension study is consistent with that of injectable SRLs but without injection-related AEs.
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Kumar, Ankit, Manisha Bharti, and Tanya Kumar. "Performance Investigation of 2-D Optical Orthogonal Codes for OCDMA." Journal of Optical Communications 40, no. 4 (October 25, 2019): 455–62. http://dx.doi.org/10.1515/joc-2017-0112.
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Abstract In this paper, comparative analysis of code performance of dissimilar optical 2-D codes from Optical Orthogonal code family has been studied. Optical 2-D codes considered from OOC family are (n,w,1,2) OOC, SPS/OOC, OCFHC/OOC, EPC/OCS and VWOOC. By utilizing hard limiting error probability (HEP) equations and combinatorial method, code performance of each considered code is evaluated in detail. On the basis of detailed comparative performance analysis, EPC/OCS is concluded as best performing codes among all other optical codes under consideration. EPC/OCS possesses much better correlation properties, along with lower hit probability values which are responsible for its supremacy in performance characteristics to the other OOCs considered.
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Rebbeck, T. R., T. M. Friebel, and S. M. Domchek. "Occult ovarian cancers at the time of risk-reducing salpingo-oophorectomy in a prospective cohort of BRCA1/2 mutation carriers." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 1508. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.1508.
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1508 Background: Risk-reducing salpingo-oophorectomy (RRSO) is widely used for cancer risk reduction in women with BRCA1 or BRCA2 (BRCA1/2) mutations. Occult ovarian cancers (OOC) detected at the time of RRSO have been reported, but there is wide variability in reported prevalence rates. Methods: We evaluated a prospective cohort of 647 women from 18 centers who underwent RRSO between 2001 and 2007 after a positive genetic test for disease-associated BRCA1/2 mutations. We estimated the prevalence of OOC. Results: Mean follow-up from genetic testing to RRSO was 1.01 years. OOC was detected in 16 of 647 women (2%). The mean age of women in whom OOC was detected was 51.7 versus 46.6 in women undergoing RRSO in whom OOC was not detected (p = 0.017). Twelve of the 16 OOCs (75%) were diagnosed in women with a BRCA1 mutation. Two OOCs were detected on RRSO prior to age 40, both in BRCA1 mutation carriers. Thirty eight percent of women with OOC had stage I cancer, as opposed to 10% of women in the PROSE database diagnosed with ovarian cancer outside of screening (p = 0.006). Among the 283 women in whom pathology reports were available for central review, 71% of RRSO were performed at the respective PROSE sites (i.e. major genetic referral centers), while 29% of RRSO were performed at local sites (i.e. community hospitals). Ovarian and fallopian tube tissues removed at RRSO at major genetics referral centers were significantly more likely to have been examined in toto compared to specimens obtained at nonreferral centers (76% vs. 24%, p < 0.001). Conclusions: RRSO reduces cancer risk and mortality in BRCA1/2 mutation carriers. Our results confirm that OOC is present at RRSO in BRCA1/2 mutation carriers, and suggest that OOC are more frequent after age 40 and are of a more favorable stage than cancers found outside the context of RRSO. Despite the fact that we examined surgeries after 2001, an unacceptably high proportion of pathologic examinations did not adequately examine ovaries and fallopian tubes obtained at RRSO. Failure to perform adequate pathological examination may overlook OOC and have clinical consequences for women undergoing RRSO. No significant financial relationships to disclose.
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Fleseriu, Maria, Akexander V. Dreval, Yulia Pokramovich, Irina Bondar, Elena Isaeva, Mark E. Molitch, Djuro P. Macut, et al. "Addition of Cabergoline to Oral Octreotide Capsules May Improve Biochemical Control in Patients With Acromegaly Who Are Inadequately Controlled With Monotherapy." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A518—A519. http://dx.doi.org/10.1210/jendso/bvab048.1058.
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Abstract Background: Oral octreotide capsules (OOC; MYCAPSSA®) are approved in the US for individuals with acromegaly who responded to and tolerated treatment with injectable somatostatin receptor ligands (iSRLs). Add-on cabergoline therapy has shown effectiveness in patients previously inadequately controlled with iSRLS.1 The phase 3 MPOWERED trial assessed maintenance of response with OOC compared to iSRLs. Patients receiving OOC and ineligible for randomized controlled treatment (RCT) phase were eligible for a sub-study evaluating combination therapy with cabergoline, a dopamine agonist. Methods: Patients who fail to respond to 80 mg/d OOC for ≥2 weeks during the 26-week Run-in phase, or ineligible to enter the RCT on 80 mg/d OOC, due to inadequate biochemical control (insulin-like growth factor I [IGF-I] ≥1.3 × upper limit of normal [ULN] to <2 × ULN or IGF-I <1.3 × ULN and mean integrated growth hormone [GH] ≥2.5 ng/mL) were eligible for sub-study combination OOC 80 mg/d and cabergoline ≤3.5 mg/wk (fixed algorithm) for 36 weeks. End points included categorical changes in IGF-I and mean GH levels at sub-study end and adverse event (AE) incidence and severity. Echocardiogram was performed at sub-study start and every 12 weeks after. Results: Of 146 patients enrolled in MPOWERED, 14 entered the combination sub-study, 9 having IGF-I ≥1.3 × ULN at sub-study start. Final cabergoline doses were 1 (n=5), 2 (n=3), 3 (n=1), and 3.5 mg (n=5) with 25.4-week (SD, 14.1) mean treatment duration. Week 36 IGF-I improved in most patients (n=12; 85.7%). Of 9 patients with IGF-I ≥1.3 × ULN at sub-study start, 5 (55.6%; 95% CI, 21.2%-86.3%) exhibited IGF-I decreased to predefined responder range (<1.3 × ULN) by week 36. AE incidence and nature with combined treatment were similar to known octreotide safety profile and acromegaly disease burden. There were no serious AEs or AEs leading to discontinuation of either sub-study drug. Conclusion: We have shown for the first time the benefit of an all-oral combination treatment for acromegaly and avoidance of injection-related burdens. Addition of cabergoline to OOC yielded biochemical control improvement (IGF-I reduction) in patients inadequately controlled with OOC monotherapy. As both combination and OOC monotherapy safety profiles were similar, adjunctive cabergoline may be helpful in patients with acromegaly who do not achieve adequate biochemical control on OOC alone. 1Giustina A, et al. Nat Rev Endocrinol. 2014;10(4):243-248.
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Pichler, S., P. Gonczy, H. Schnabel, A. Pozniakowski, A. Ashford, R. Schnabel, and A. A. Hyman. "OOC-3, a novel putative transmembrane protein required for establishment of cortical domains and spindle orientation in the P(1) blastomere of C. elegans embryos." Development 127, no. 10 (May 15, 2000): 2063–73. http://dx.doi.org/10.1242/dev.127.10.2063.
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Asymmetric cell divisions require the establishment of an axis of polarity, which is subsequently communicated to downstream events. During the asymmetric cell division of the P(1) blastomere in C. elegans, establishment of polarity depends on the establishment of anterior and posterior cortical domains, defined by the localization of the PAR proteins, followed by the orientation of the mitotic spindle along the previously established axis of polarity. To identify genes required for these events, we have screened a collection of maternal-effect lethal mutations on chromosome II of C. elegans. We have identified a mutation in one gene, ooc-3, with mis-oriented division axes at the two-cell stage. Here we describe the phenotypic and molecular characterization of ooc-3. ooc-3 is required for the correct localization of PAR-2 and PAR-3 cortical domains after the first cell division. OOC-3 is a novel putative transmembrane protein, which localizes to a reticular membrane compartment, probably the endoplasmic reticulum, that spans the whole cytoplasm and is enriched on the nuclear envelope and cell-cell boundaries. Our results show that ooc-3 is required to form the cortical domains essential for polarity after cell division.
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Azizipour, Neda, Rahi Avazpour, Derek H. Rosenzweig, Mohamad Sawan, and Abdellah Ajji. "Evolution of Biochip Technology: A Review from Lab-on-a-Chip to Organ-on-a-Chip." Micromachines 11, no. 6 (June 18, 2020): 599. http://dx.doi.org/10.3390/mi11060599.
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Following the advancements in microfluidics and lab-on-a-chip (LOC) technologies, a novel biomedical application for microfluidic based devices has emerged in recent years and microengineered cell culture platforms have been created. These micro-devices, known as organ-on-a-chip (OOC) platforms mimic the in vivo like microenvironment of living organs and offer more physiologically relevant in vitro models of human organs. Consequently, the concept of OOC has gained great attention from researchers in the field worldwide to offer powerful tools for biomedical researches including disease modeling, drug development, etc. This review highlights the background of biochip development. Herein, we focus on applications of LOC devices as a versatile tool for POC applications. We also review current progress in OOC platforms towards body-on-a-chip, and we provide concluding remarks and future perspectives for OOC platforms for POC applications.
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Guenat, Olivier T., Thomas Geiser, and François Berthiaume. "Clinically Relevant Tissue Scale Responses as New Readouts from Organs-on-a-Chip for Precision Medicine." Annual Review of Analytical Chemistry 13, no. 1 (June 12, 2020): 111–33. http://dx.doi.org/10.1146/annurev-anchem-061318-114919.
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Organs-on-chips (OOC) are widely seen as being the next generation in vitro models able to accurately recreate the biochemical-physical cues of the cellular microenvironment found in vivo. In addition, they make it possible to examine tissue-scale functional properties of multicellular systems dynamically and in a highly controlled manner. Here we summarize some of the most remarkable examples of OOC technology's ability to extract clinically relevant tissue-level information. The review is organized around the types of OOC outputs that can be measured from the cultured tissues and transferred to clinically meaningful information. First, the creation of functional tissues-on-chip is discussed, followed by the presentation of tissue-level readouts specific to OOC, such as morphological changes, vessel formation and function, tissue properties, and metabolic functions. In each case, the clinical relevance of the extracted information is highlighted.
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Sonawane, Heena, Freny R. Karjodkar, Kaustubh Sansare, and Nimish Prakash. "Orthokeratinized Odontogenic Cyst: A Rarity." An International Journal of Otorhinolaryngology Clinics 6, no. 3 (2014): 23–27. http://dx.doi.org/10.5005/aijoc-6-3-23.
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ABSTRACT Orthokeratinized odontogenic cyst (OOC) was first identified as the rare variant of keratocystic odontogenic tumor (KCOT) for its different histopathology and rare recurrence which was reclassified by WHO in 2005. The orthokeratinized odontogenic cyst is a distinct clinicopathologic entity and is histologically characterized by a thin, uniform, epithelial lining with orthokeratinization and a subjacent granular cell layer. The basal cells are usually cuboidal or flattened. OOC in maxilla is rare. This article presents a case of 56-years-old male patient with OOC in left maxilla. The clinical, radiographic and histological features of the cyst are discussed in this case report.
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Dong, Qing, Shuang Pan, Li-Sha Sun, and Tie-Jun Li. "Orthokeratinized Odontogenic Cyst: A Clinicopathologic Study of 61 Cases." Archives of Pathology & Laboratory Medicine 134, no. 2 (February 1, 2010): 271–75. http://dx.doi.org/10.5858/134.2.271.
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Abstract Context.—Orthokeratinized odontogenic cyst (OOC) is a relatively uncommon developmental cyst comprising about 10% of cases that had been previously coded as odontogenic keratocysts. Odontogenic keratocyst was designated as keratocystic odontogenic tumor (KCOT) in the new World Health Organization classification and OOC should be distinguished from KCOT for differences in histologic features and biologic behavior. Objective.—To analyze the clinicopathologic features of 61 cases of OOC in a Chinese population. Design.—Clinicopathologic analysis was performed on 61 cases of OOC. Immunohistochemical expression of Ki-67 and p63 was evaluated in 15 OOCs and 15 typical KCOTs. Results.—The 61 patients with OOC ranged from 13 to 75 years (average, 38.93 years). The lesions developed mainly in the third and fourth decades (57.38%) with a distinct predilection for males (72.13%). Six (9.84%) lesions were found in the maxilla and 55 (90.16%) in the mandible. The most common sites were in the mandibular molar and ramus region. Of the 54 cases with radiographic record, 47 (87.04%) were unilocular and 7 (12.96%) were multilocular radiolucencies. Twenty-seven of the 54 cysts were associated with an impacted tooth. Follow-up of 42 patients revealed no recurrence during an average period of 76.8 months after surgery. Compared with KCOTs, expression level of Ki-67 and p63 was significantly lower in OOCs, suggesting a lower proliferative activity. Conclusion.—Orthokeratinized odontogenic cyst is clinicopathologically distinct from KCOT and should constitute its own clinical entity.
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Akarapipad, Patarajarin, Kattika Kaarj, Yan Liang, and Jeong-Yeol Yoon. "Environmental Toxicology Assays Using Organ-on-Chip." Annual Review of Analytical Chemistry 14, no. 1 (June 5, 2021): 155–83. http://dx.doi.org/10.1146/annurev-anchem-091620-091335.
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Adverse effects of environmental toxicants to human health have traditionally been assayed using in vitro assays. Organ-on-chip (OOC) is a new platform that can bridge the gaps between in vitro assays (or 3D cell culture) and animal tests. Microenvironments, physical and biochemical stimuli, and adequate sensing and biosensing systems can be integrated into OOC devices to better recapitulate the in vivo tissue and organ behavior and metabolism. While OOCs have extensively been studied for drug toxicity screening, their implementation in environmental toxicology assays is minimal and has limitations. In this review, recent attempts of environmental toxicology assays using OOCs, including multiple-organs-on-chip, are summarized and compared with OOC-based drug toxicity screening. Requirements for further improvements are identified and potential solutions are suggested.
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Zhu, Li, James O. Wrabl, Adam P. Hayashi, Lesilee S. Rose, and Philip J. Thomas. "The Torsin-family AAA+ Protein OOC-5 Contains a Critical Disulfide Adjacent to Sensor-II That Couples Redox State to Nucleotide Binding." Molecular Biology of the Cell 19, no. 8 (August 2008): 3599–612. http://dx.doi.org/10.1091/mbc.e08-01-0015.
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A subgroup of the AAA+ proteins that reside in the endoplasmic reticulum and the nuclear envelope including human torsinA, a protein mutated in hereditary dystonia, is called the torsin family of AAA+ proteins. A multiple-sequence alignment of this family with Hsp100 proteins of known structure reveals a conserved cysteine in the C-terminus of torsin proteins within the Sensor-II motif. A structural model predicts this cysteine to be a part of an intramolecular disulfide bond, suggesting that it may function as a redox sensor to regulate ATPase activity. In vitro experiments with OOC-5, a torsinA homolog from Caenorhabditis elegans, demonstrate that redox changes that reduce this disulfide bond affect the binding of ATP and ADP and cause an attendant local conformational change detected by limited proteolysis. Transgenic worms expressing an ooc-5 gene with cysteine-to-serine mutations that disrupt the disulfide bond have a very low embryo hatch rate compared with wild-type controls, indicating these two cysteines are essential for OOC-5 function. We propose that the Sensor-II in torsin family proteins is a redox-regulated sensor. This regulatory mechanism may be central to the function of OOC-5 and human torsinA.
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VanGompel, Michael J. W., Ken C. Q. Nguyen, David H. Hall, William T. Dauer, and Lesilee S. Rose. "A novel function for the Caenorhabditis elegans torsin OOC-5 in nucleoporin localization and nuclear import." Molecular Biology of the Cell 26, no. 9 (May 2015): 1752–63. http://dx.doi.org/10.1091/mbc.e14-07-1239.
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Torsin proteins are AAA+ ATPases that localize to the endoplasmic reticular/nuclear envelope (ER/NE) lumen. A mutation that markedly impairs torsinA function causes the CNS disorder DYT1 dystonia. Abnormalities of NE membranes have been linked to torsinA loss of function and the pathogenesis of DYT1 dystonia, leading us to investigate the role of the Caenorhabditis elegans torsinA homologue OOC-5 at the NE. We report a novel role for torsin in nuclear pore biology. In ooc-5–mutant germ cell nuclei, nucleoporins (Nups) were mislocalized in large plaques beginning at meiotic entry and persisted throughout meiosis. Moreover, the KASH protein ZYG-12 was mislocalized in ooc-5 gonads. Nups were mislocalized in adult intestinal nuclei and in embryos from mutant mothers. EM analysis revealed vesicle-like structures in the perinuclear space of intestinal and germ cell nuclei, similar to defects reported in torsin-mutant flies and mice. Consistent with a functional disruption of Nups, ooc-5–mutant embryos displayed impaired nuclear import kinetics, although the nuclear pore-size exclusion barrier was maintained. Our data are the first to demonstrate a requirement for a torsin for normal Nup localization and function and suggest that these functions are likely conserved.
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Fowler, Carol A. "The orderly output constraint is not wearing any clothes." Behavioral and Brain Sciences 21, no. 2 (April 1998): 265–66. http://dx.doi.org/10.1017/s0140525x98291175.
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The orderly output constraint (OOC) is extraneous. Talkers “speak in lines” in its absence. Further, there is no perceptual motivation for an OOC; perceivers ignore the linearity between F2 at consonant-vowel onset and F2 in the vowel. In any case, the analogy with bat and barn owl localization systems underlying the theory is extreme, Sussman et al.'s comments to the contrary notwithstanding.
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Cyr, Kevin J., Omero M. Avaldi, and John P. Wikswo. "Circadian hormone control in a human-on-a-chip: In vitro biology’s ignored component?" Experimental Biology and Medicine 242, no. 17 (October 25, 2017): 1714–31. http://dx.doi.org/10.1177/1535370217732766.
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Organs-on-Chips (OoCs) are poised to reshape dramatically the study of biology by replicating in vivo the function of individual and coupled human organs. Such microphysiological systems (MPS) have already recreated complex physiological responses necessary to simulate human organ function not evident in two-dimensional in vitro biological experiments. OoC researchers hope to streamline pharmaceutical development, accelerate toxicology studies, limit animal testing, and provide new insights beyond the capability of current biological models. However, to develop a physiologically accurate Human-on-a-Chip, i.e., an MPS homunculus that functions as an interconnected, whole-body, model organ system, one must couple individual OoCs with proper fluidic and metabolic scaling. This will enable the study of the effects of organ-organ interactions on the metabolism of drugs and toxins. Critical to these efforts will be the recapitulation of the complex physiological signals that regulate the endocrine, metabolic, and digestive systems. To date, with the exception of research focused on reproductive organs on chips, most OoC research ignores homuncular endocrine regulation, in particular the circadian rhythms that modulate the function of all organ systems. We outline the importance of cyclic endocrine regulation and the role that it may play in the development of MPS homunculi for the pharmacology, toxicology, and systems biology communities. Moreover, we discuss the critical end-organ hormone interactions that are most relevant for a typical coupled-OoC system, and the possible research applications of a missing endocrine system MicroFormulator (MES-µF) that could impose biological rhythms on in vitro models. By linking OoCs together through chemical messenger systems, advanced physiological phenomena relevant to pharmacokinetics and pharmacodynamics studies can be replicated. The concept of a MES-µF could be applied to other standard cell-culture systems such as well plates, thereby extending the concept of circadian hormonal regulation to much of in vitro biology. Impact statement Historically, cyclic endocrine modulation has been largely ignored within in vitro cell culture, in part because cultured cells typically have their media changed every day or two, precluding hourly adjustment of hormone concentrations to simulate circadian rhythms. As the Organ-on-Chip (OoC) community strives for greater physiological realism, the contribution of hormonal oscillations toward regulation of organ systems has been examined only in the context of reproductive organs, and circadian variation of the breadth of other hormones on most organs remains unaddressed. We illustrate the importance of cyclic endocrine modulation and the role that it plays within individual organ systems. The study of cyclic endocrine modulation within OoC systems will help advance OoC research to the point where it can reliably replicate in vitro key regulatory components of human physiology. This will help translate OoC work into pharmaceutical applications and connect the OoC community with the greater pharmacology and physiology communities.
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Sonawane, Heena, Freny R. Karjodkar, Kaustubh Sansare, and Nimish Prakash. "Orthokeratinized Odontogenic Cyst: A Rarity." An International Journal of Otorhinolaryngology Clinics 5, no. 3 (2013): 182–86. http://dx.doi.org/10.5005/jp-journals-10003-1140.
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ABSTRACT Orthokeratinized odontogenic cyst (OOC) was first identified as the rare variant of keratocystic odontogenic tumor (KCOT) for its different histopathology and rare recurrence which was reclassified by WHO in 2005. The orthokeratinized odontogenic cyst is a distinct clinicopathologic entity and is histologically characterized by a thin, uniform, epithelial lining with orthokeratinization and a subjacent granular cell layer. The basal cells are usually cuboidal or flattened. OOC in maxilla is rare. This article presents a case of 56-years-old male patient with OOC in left maxilla. The clinical, radiographic and histological features of the cyst are discussed in this case report. How to cite this article Sonawane H, Karjodkar FR, Sansare K, Prakash N. Orthokeratinized Odontogenic Cyst: A Rarity. Int J Otorhinolaryngol Clin 2013;5(3):182-186.
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Sharma, Swati, Bastien Venzac, Thomas Burgers, Séverine Le Gac, and Stefan Schlatt. "Microfluidics in male reproduction: is ex vivo culture of primate testis tissue a future strategy for ART or toxicology research?" Molecular Human Reproduction 26, no. 3 (January 16, 2020): 179–92. http://dx.doi.org/10.1093/molehr/gaaa006.
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Abstract The significant rise in male infertility disorders over the years has led to extensive research efforts to recapitulate the process of male gametogenesis in vitro and to identify essential mechanisms involved in spermatogenesis, notably for clinical applications. A promising technology to bridge this research gap is organ-on-chip (OoC) technology, which has gradually transformed the research landscape in ART and offers new opportunities to develop advanced in vitro culture systems. With exquisite control on a cell or tissue microenvironment, customized organ-specific structures can be fabricated in in vitro OoC platforms, which can also simulate the effect of in vivo vascularization. Dynamic cultures using microfluidic devices enable us to create stimulatory effect and non-stimulatory culture conditions. Noteworthy is that recent studies demonstrated the potential of continuous perfusion in OoC systems using ex vivo mouse testis tissues. Here we review the existing literature and potential applications of such OoC systems for male reproduction in combination with novel bio-engineering and analytical tools. We first introduce OoC technology and highlight the opportunities offered in reproductive biology in general. In the subsequent section, we discuss the complex structural and functional organization of the testis and the role of the vasculature-associated testicular niche and fluid dynamics in modulating testis function. Next, we review significant technological breakthroughs in achieving in vitro spermatogenesis in various species and discuss the evidence from microfluidics-based testes culture studies in mouse. Lastly, we discuss a roadmap for the potential applications of the proposed testis-on-chip culture system in the field of primate male infertility, ART and reproductive toxicology.
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Mandenius, Carl-Fredrik. "Conceptual Design of Micro-Bioreactors and Organ-on-Chips for Studies of Cell Cultures." Bioengineering 5, no. 3 (July 19, 2018): 56. http://dx.doi.org/10.3390/bioengineering5030056.
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Engineering design of microbioreactors (MBRs) and organ-on-chip (OoC) devices can take advantage of established design science theory, in which systematic evaluation of functional concepts and user requirements are analyzed. This is commonly referred to as a conceptual design. This review article compares how common conceptual design principles are applicable to MBR and OoC devices. The complexity of this design, which is exemplified by MBRs for scaled-down cell cultures in bioprocess development and drug testing in OoCs for heart and eye, is discussed and compared with previous design solutions of MBRs and OoCs, from the perspective of how similarities in understanding design from functionality and user purpose perspectives can more efficiently be exploited. The review can serve as a guideline and help the future design of MBR and OoC devices for cell culture studies.
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Samson, Susan L., Lisa B. Nachtigall, Maria Fleseriu, Murray B. Gordon, Marek Bolanowski, Artak Labadzhyan, Ehud Ur, et al. "Maintenance of Acromegaly Control in Patients Switching From Injectable Somatostatin Receptor Ligands to Oral Octreotide." Journal of Clinical Endocrinology & Metabolism 105, no. 10 (August 16, 2020): e3785-e3797. http://dx.doi.org/10.1210/clinem/dgaa526.
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Abstract Purpose The phase 3 CHIASMA OPTIMAL trial (NCT03252353) evaluated efficacy and safety of oral octreotide capsules (OOCs) in patients with acromegaly who previously demonstrated biochemical control while receiving injectable somatostatin receptor ligands (SRLs). Methods In this double-blind study, patients (N = 56) stratified by prior SRL dose were randomly assigned 1:1 to OOC or placebo for 36 weeks. The primary end point was maintenance of biochemical control at the end of treatment (mean insulin-like growth factor 1 [IGF-1] ≤ 1.0 × upper limit of normal [ULN]; weeks 34 and 36). Time to loss of IGF-1 response and proportion requiring reversion to injectable SRLs were assessed as broader control measures. Results Mean IGF-1 measurements were 0.80 and 0.97 × ULN for OOC and 0.84 and 1.69 × ULN for placebo, at baseline and end of treatment, respectively. Mean growth hormone (GH) changed from 0.66 to 0.60 ng/mL for OOCs and 0.90 to 2.57 ng/mL for placebo. Normalization of IGF-1 levels (≤ 1.0 × ULN) was maintained in 58.2% for OOCs vs 19.4% for placebo (P = .008); GH levels were maintained (< 2.5 ng/mL) in 77.7% for OOC vs 30.4% for placebo (P = .0007). Median time to loss of response (IGF-1 > 1.0 or ≥ 1.3 × ULN definitions) for patients receiving placebo was 16 weeks; for patients receiving OOCs, it was not reached for both definitions during the 36-week trial (P < .0001). Of the patients in the OOC group, 75% completed the trial on oral therapy. The OOC safety profile was consistent with previous SRL experience. Conclusions OOCs may be an effective therapy for patients with acromegaly who previously were treated with injectable SRLs.
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Chu, Wensong, and Charles J. Colbourn. "Optimal (n,4,2)-OOC of small orders." Discrete Mathematics 279, no. 1-3 (March 2004): 163–72. http://dx.doi.org/10.1016/s0012-365x(03)00266-8.
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Wang, Guangguo, Yongquan Zhou, He Lin, Zhuanfang Jing, Hongyan Liu, and Fayan Zhu. "Structure of aqueous sodium acetate solutions by X-Ray scattering and density functional theory." Pure and Applied Chemistry 92, no. 10 (October 25, 2020): 1627–41. http://dx.doi.org/10.1515/pac-2020-0402.
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AbstractThe structure of aq. sodium acetate solution (CH3COONa, NaOAc) was studied by X-ray scattering and density function theory (DFT). For the first hydrated layer of Na+, coordination number (CN) between Na+ and O(W, I) decreases from 5.02 ± 0.85 at 0.976 mol/L to 3.62 ± 1.21 at 4.453 mol/L. The hydration of carbonyl oxygen (OC) and hydroxyl oxygen (OOC) of CH3COO− were investigated separately and the OC shows a stronger hydration bonds comparing with OOC. With concentrations increasing, the hydration shell structures of CH3COO− are not affected by the presence of large number of ions, each CH3COO− group binds about 6.23 ± 2.01 to 7.35 ± 1.73 water molecules, which indicates a relatively strong interaction between CH3COO− and water molecules. The larger uncertainty of the CN of Na+ and OC(OOC) reflects the relative looseness of Na-OC and Na-OOC ion pairs in aq. NaOAc solutions, even at the highest concentration (4.453 mol/L), suggesting the lack of contact ion pair (CIP) formation. In aq. NaOAc solutions, the so called “structure breaking” property of Na+ and CH3COO− become effective only for the second hydration sphere of bulk water. The DFT calculations of CH3COONa (H2O)n=5–7 clusters suggest that the solvent-shared ion pair (SIP) structures appear at n = 6 and become dominant at n = 7, which is well consistent with the result from X-ray scattering.
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Berasategui, Matias, Maximiliano A. Burgos Paci, and Gustavo A. Argüello. "Isolation and Characterization of CH3OC(O)OOC(O)F from the Reaction CH3OH + FC(O)OOC(O)F." Zeitschrift für anorganische und allgemeine Chemie 638, no. 3-4 (December 19, 2011): 547–52. http://dx.doi.org/10.1002/zaac.201100404.
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Wu, Xue Ying, Ying Meng, and Peng Liu. "Study on Indoor 2D-OCDMA VLC System." Applied Mechanics and Materials 303-306 (February 2013): 2038–41. http://dx.doi.org/10.4028/www.scientific.net/amm.303-306.2038.
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We propose visible light communication 2D-OCDMA system for indoor communication. We first discuss about the system model, and also discuss about the construct of 2D-OOC code with 2-D OCDMA VLC system and 2-D OCDMA VLC with MWOOC. Compare it with 1D OOC. And we also give some analysis the capacity of 2D-OCDMA in VLC. From the analysis the structure of the 2D-OCDMA is complicated but using 2D-OCDMA can enhance the capacity of the system in the room. More work should be done in the future on this research.
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Clapp, Naomi, Augustin Amour, Wendy C. Rowan, and Pelin L. Candarlioglu. "Organ-on-chip applications in drug discovery: an end user perspective." Biochemical Society Transactions 49, no. 4 (August 16, 2021): 1881–90. http://dx.doi.org/10.1042/bst20210840.
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Organ-on-chip (OoC) systems are in vitro microfluidic models that mimic the microstructures, functions and physiochemical environments of whole living organs more accurately than two-dimensional models. While still in their infancy, OoCs are expected to bring ground-breaking benefits to a myriad of applications, enabling more human-relevant candidate drug efficacy and toxicity studies, and providing greater insights into mechanisms of human disease. Here, we explore a selection of applications of OoC systems. The future directions and scope of implementing OoCs across the drug discovery process are also discussed.
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Luttge, Regina. "Editorial for the Special Issue on Microfluidic Brain-on-a-Chip." Micromachines 12, no. 9 (September 13, 2021): 1100. http://dx.doi.org/10.3390/mi12091100.
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Asif, Muhammad, Wuyang Zhou, Qingping Yu, Xingwang Li, and Nauman Ali Khan. "A Deterministic Construction for Jointly Designed Quasicyclic LDPC Coded-Relay Cooperation." Wireless Communications and Mobile Computing 2019 (September 26, 2019): 1–12. http://dx.doi.org/10.1155/2019/5249373.
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This correspondence presents a jointly designed quasicyclic (QC) low-density parity-check (LDPC) coded-relay cooperation with joint-iterative decoding in the destination node. Firstly, a design-theoretic construction of QC-LDPC codes based on a combinatoric design approach known as optical orthogonal codes (OOC) is presented. Proposed OOC-based construction gives three classes of binary QC-LDPC codes with no length-4 cycles by utilizing some known ingredients including binary matrix dispersion of elements of finite field, incidence matrices, and circulant decomposition. Secondly, the proposed OOC-based construction gives an effective method to jointly design length-4 cycles free QC-LDPC codes for coded-relay cooperation, where sum-product algorithm- (SPA-) based joint-iterative decoding is used to decode the corrupted sequences coming from the source or relay nodes in different time frames over constituent Rayleigh fading channels. Based on the theoretical analysis and simulation results, proposed QC-LDPC coded-relay cooperations outperform their competitors under same conditions over the Rayleigh fading channel with additive white Gaussian noise.
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Zhao, Qianbin, Tim Cole, Yuxin Zhang, and Shi-Yang Tang. "Mechanical Strain-Enabled Reconstitution of Dynamic Environment in Organ-on-a-Chip Platforms: A Review." Micromachines 12, no. 7 (June 28, 2021): 765. http://dx.doi.org/10.3390/mi12070765.
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Organ-on-a-chip (OOC) uses the microfluidic 3D cell culture principle to reproduce organ- or tissue-level functionality at a small scale instead of replicating the entire human organ. This provides an alternative to animal models for drug development and environmental toxicology screening. In addition to the biomimetic 3D microarchitecture and cell–cell interactions, it has been demonstrated that mechanical stimuli such as shear stress and mechanical strain significantly influence cell behavior and their response to pharmaceuticals. Microfluidics is capable of precisely manipulating the fluid of a microenvironment within a 3D cell culture platform. As a result, many OOC prototypes leverage microfluidic technology to reproduce the mechanically dynamic microenvironment on-chip and achieve enhanced in vitro functional organ models. Unlike shear stress that can be readily generated and precisely controlled using commercial pumping systems, dynamic systems for generating proper levels of mechanical strains are more complicated, and often require miniaturization and specialized designs. As such, this review proposes to summarize innovative microfluidic OOC platforms utilizing mechanical actuators that induce deflection of cultured cells/tissues for replicating the dynamic microenvironment of human organs.
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Fainassi, Firdaous, Noamane Taarji, Fatiha Benkhalti, Abdellatif Hafidi, Marcos A. Neves, Hiroko Isoda, and Mitsutoshi Nakajima. "Emulsion Formation and Stabilizing Properties of Olive Oil Cake Crude Extracts." Processes 9, no. 4 (April 4, 2021): 633. http://dx.doi.org/10.3390/pr9040633.
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The surface-active and emulsifying properties of crude aqueous ethanolic extracts from untreated olive oil cake (OOC) were investigated. OOC extracts contained important concentrations of surface-active components including proteins, saponins and polyphenols (1.2–2.8%, 7.8–9.5% and 0.7–4.5% (w/w), respectively) and reduced the interfacial tension by up to 46% (14.0 ± 0.2 mN m−1) at the oil–water interface. The emulsifying ability of OOC extracts was not correlated, however, with their interfacial activity or surface-active composition. Eighty percent aqueous ethanol extract produced the most stable oil-in-water (O/W) emulsions by high-pressure homogenization. The emulsions had average volume mean droplet diameters of approximately 0.4 µm and negative ζ-potentials of about −45 mV, and were stable for up to 1 month of storage at 5, 25 and 50 °C. They were sensitive, however, to acidic pH conditions (<5) and NaCl addition (≥25 mM), indicating that the main stabilization mechanism is electrostatic due to the presence of surface-active compounds with ionizable groups, such as saponins.
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Kopitzky, Rodion, Helge Willner, Angelika Hermann, and Heinz Oberhammer. "Bis(trifluoroacetyl) Peroxide, CF3C(O)OOC(O)CF3." Inorganic Chemistry 40, no. 12 (June 2001): 2693–98. http://dx.doi.org/10.1021/ic0014639.
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Li, Xiaobin, and Tingting Fu. "OOC constructing algorithm based on outer-product matrix." Procedia Engineering 15 (2011): 2308–12. http://dx.doi.org/10.1016/j.proeng.2011.08.432.
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Meadows, Shatori, Mahesh Hosur, Yusuf Celikbag, and Shaik Jeelani. "Comparative Analysis on the Epoxidation of Soybean Oil using Formic and Acetic Acids." Polymers and Polymer Composites 26, no. 4 (May 2018): 289–98. http://dx.doi.org/10.1177/096739111802600403.
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The objective of this study was to make a comparative analysis of the effect of formic and acetic acids as oxygen carriers on the epoxidation of soybean oil used with hydrogen peroxide as the oxygen donor. Comparative analysis between the use of formic acid (FA) and acetic acid (AA) was studied to obtain the most effective oxygen carrier that yielded high oxirane oxygen contents (OOC). The epoxidation reaction was carried out using a stoichiometric ratio of 1:0.5:1, 1:0.5:0.5, and 1:0.5:2 of soybean oil: formic/acetic acid: hydrogen peroxide. The synthesis was performed at three reaction times (2, 4 and 6 h) at a constant temperature of 50°C. Samples prepared using FA and AA were characterized using ASTM D1652-11 and confirmed by Fourier transform infrared (FTIR) spectroscopy. The result of this study proved FA to be an effective oxygen carrier compared to that of AA based on the high OOC and percent yield achieved. The optimum epoxidized soybean oil (ESO) sample using FA was obtained at a reaction time of 6 h using 2 moles of H2O2, yielding an OOC of 7.45 at a relative conversion to oxirane of 98%. Samples of FA were further characterized to prove the optimum parameters that gave the highest OOC using rheology and gel permeation chromatography (GPC). Rheology data revealed an increase in the viscosity that implied an increase in the degree of epoxidation. GPC indicated an increase in the molecular weight at low reaction times, then a decrease resulting in a change in the structure of the triglyceride and consequently an increase in the extent of epoxidation.
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Jiang, Xiaoyu, Takashi Matsushima, and Raphael Blumenfeld. "Structural characteristics of ordered clusters in packs of ellipses." EPJ Web of Conferences 249 (2021): 06004. http://dx.doi.org/10.1051/epjconf/202124906004.
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Structural characteristics of two-dimensional elliptic granular packs with various aspect ratios and intergranular friction coefficients were studied using the Discrete Element Method (DEM). Isotropic compaction from random unjammed state leads to a jammed state with polycrystals of orientationally ordered clusters (OOC). The OOCs were identified using a cluster labelling algorithm, based on the relative angle Δθ between the major axes of two contacting particles. The threshold value of Δθ was optimised to give the strongest correlation between OOCs and the force chain network. We found that the resulting OOC size distribution decays algebraically with an exponent of −2, independently of grain aspect ratio and material properties.
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Carvalho, Cyntia Helena Pereira de, Ana Rafaela Luz de Aquino, Cassiano Francisco Weege Nonaka, José Sandro Pereira da Silva, Adriano da Rocha Germano, and Leão Pereira Pinto. "Infected orthokeratinized odontogenic cyst: a rare cause of facial cellulitis." Brazilian Dental Journal 23, no. 5 (October 2012): 612–16. http://dx.doi.org/10.1590/s0103-64402012000500025.
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Orthokeratinized odontogenic cysts (OOCs) are relatively uncommon developmental cysts lined with orthokeratinized epithelium consisting of a prominent granular layer and a basal layer of low cuboidal flattened cells that show no tendency for nuclear palisading. These cysts have been considered a distinct entity from odontogenic keratocysts since they exhibit a less aggressive behavior and a very low rate of recurrence. Developmental odontogenic cysts can become infected but serious complications, such as potentially life-threatening cellulitis, are rare. This report describes a rare case of facial cellulitis secondary to an infected OOC located in the mandible of a 27-year-old man. The relevant literature about the clinical-pathological features of OOC is reviewed.
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Tang, Li, Xia Luo, Yang Cheng, Fei Yang, and Bin Ran. "Comparing the State-of-the-Art Efficient Stated Choice Designs Based on Empirical Analysis." Mathematical Problems in Engineering 2014 (2014): 1–8. http://dx.doi.org/10.1155/2014/740612.
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The stated choice (SC) experiment has been generally regarded as an effective method for behavior analysis. Among all the SC experimental design methods, the orthogonal design has been most widely used since it is easy to understand and construct. However, in recent years, a stream of research has put emphasis on the so-called efficient experimental designs rather than keeping the orthogonality of the experiment, as the former is capable of producing more efficient data in the sense that more reliable parameter estimates can be achieved with an equal or lower sample size. This paper provides two state-of-the-art methods called optimal orthogonal choice (OOC) andD-efficient design. More statistically efficient data is expected to be obtained by either maximizing attribute level differences, or minimizing theD-error, a statistic corresponding to the asymptotic variance-covariance (AVC) matrix of the discrete choice model, when using these two methods, respectively. Since comparison and validation in the field of these methods are rarely seen, an empirical study is presented.D-error is chosen as the measure of efficiency. The result shows that both OOC andD-efficient design are more efficient. At last, strength and weakness of orthogonal, OOC, andD-efficient design are summarized.
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Paoli, Roberto, Davide Di Giuseppe, Maider Badiola-Mateos, Eugenio Martinelli, Maria Jose Lopez-Martinez, and Josep Samitier. "Rapid Manufacturing of Multilayered Microfluidic Devices for Organ on a Chip Applications." Sensors 21, no. 4 (February 16, 2021): 1382. http://dx.doi.org/10.3390/s21041382.
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Microfabrication and Polydimethylsiloxane (PDMS) soft-lithography techniques became popular for microfluidic prototyping at the lab, but even after protocol optimization, fabrication is yet a long, laborious process and partly user-dependent. Furthermore, the time and money required for the master fabrication process, necessary at any design upgrade, is still elevated. Digital Manufacturing (DM) and Rapid-Prototyping (RP) for microfluidics applications arise as a solution to this and other limitations of photo and soft-lithography fabrication techniques. Particularly for this paper, we will focus on the use of subtractive DM techniques for Organ-on-a-Chip (OoC) applications. Main available thermoplastics for microfluidics are suggested as material choices for device fabrication. The aim of this review is to explore DM and RP technologies for fabrication of an OoC with an embedded membrane after the evaluation of the main limitations of PDMS soft-lithography strategy. Different material options are also reviewed, as well as various bonding strategies. Finally, a new functional OoC device is showed, defining protocols for its fabrication in Cyclic Olefin Polymer (COP) using two different RP technologies. Different cells are seeded in both sides of the membrane as a proof of concept to test the optical and fluidic properties of the device.
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Gutsanu, Vasilii, Constantin Turta, and George Filoti. "Metallic Compounds in the Phase of the Reticulated Ionic Polymers." Chemistry Journal of Moldova 5, no. 2 (December 2010): 73–82. http://dx.doi.org/10.19261/cjm.2010.05(2).10.
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Using the Mossbauer spectroscopy and other physical methods it was demonstrated the presence of different iron compounds like β-FeOOH, α-Fe2O3, and jarosite mineral type compounds: (R4N,H3O)[Fe3(OH)6(SO4)2] or coordination modes: {RCOO-Fe(L4)-OOCR}1+, {R-CO2=Fe(X2)=O2C-R}n, {R-COO-Fe(X4)-OOC-R}n, and {(-NCH2CH2N-)= Fe(X2) =(-NCH2CH2N-)}, where X= H2O, OH-, SO42-., n= from 3- to 1+ in the ion-exchange resins (KU-2, AN-31, AV-17, Varian – AD, EDE-10P) after the contact with sulphate of iron(III) solutions at different conditions: type of solvent, temperature, air atmosphere. In special conditions the ultrafine superparamagnetic particles of Fe2O3 have been obtained.