A Hybrid Model to Predict Formulation Dependent Granule Growth in a Bi-Component Wet Granulation Process

In this study, a hybrid modeling framework was developed for predicting size distribution and content uniformity of granules in a bi-component wet granulation system with components of differing hydrophobicities. Two bi-component formulations, (1) ibuprofen-USP and micro-crystalline cellulose and (2) micronized acetaminophen and micro-crystalline cellulose, were used in this study. First, a random forest method was used for predicting the probability of nucleation mechanism (immersion and solid spread), depending upon the formulation hydrophobicity. The predicted nucleation mechanism probability is used to determine the aggregation rate as well as the initial particle distribution in the population balance model. The aggregation process was modeled as Type-I: Sticking aggregation and Type-II: Deformation driven aggregation. In Type-I, the capillary force dominant aggregation mechanism is represented by the particles sticking together without deformation. In the case of Type-II, the particle deformation causes an increase in the contact area, representing a viscous force dominant aggregation mechanism. The choice between Type-I and II aggregation is determined based on the difference in nucleation mechanism that is predicted using the random forest method. The model was optimized and validated using the granule content uniformity data and size distribution data obtained from the experimental studies. The proposed framework predicted content non-uniform behavior for formulations that favored immersion nucleation and uniform behavior for formulations that favored solid-spreading nucleation.

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Altered type II interferon precedes autoantibody accrual and elevated type I interferon activity prior to systemic lupus erythematosus classification

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2015-208140 ◽

2016 ◽

Vol 75 (11) ◽

pp. 2014-2021 ◽

Cited By ~ 88

Author(s):

Melissa E Munroe ◽

Rufei Lu ◽

Yan D Zhao ◽

Dustin A Fife ◽

Julie M Robertson ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Random Forest ◽

Lupus Erythematosus ◽

Type I Interferon ◽

Type I ◽

Type Ii ◽

Systemic Lupus ◽

Forest Models ◽

Random Forest Models ◽

Α Activity

ObjectivesThe relationship of immune dysregulation and autoantibody production that may contribute to systemic lupus erythematosus (SLE) pathogenesis is unknown. This study evaluates the individual and combined contributions of autoantibodies, type I interferon (IFN-α) activity, and IFN-associated soluble mediators to disease development leading to SLE.MethodsSerial serum specimens from 55 individuals collected prior to SLE classification (average timespan=4.3 years) and unaffected healthy controls matched by age (±5 years), gender, race and time of sample procurement were obtained from the Department of Defense Serum Repository. Levels of serum IFN-α activity, IFN-associated mediators and autoantibodies were evaluated and temporal relationships assessed by growth curve modelling, path analysis, analysis of covariance and random forest models.ResultsIn cases, but not matched controls, autoantibody specificities and IFN-associated mediators accumulated over a period of years, plateauing near the time of disease classification (p<0.001). Autoantibody positivity coincided with or followed type II IFN dysregulation, preceding IFN-α activity in growth curve models, with elevated IFN-α activity and B-lymphocyte stimulator levels occurring shortly before SLE classification (p≤0.005). Cases were distinguished by multivariate random forest models incorporating IFN-γ, macrophage chemoattractant protein (MCP)-3, anti-chromatin and anti-spliceosome antibodies (accuracy 93% >4 years pre-classification; 97% within 2 years of SLE classification).ConclusionsYears before SLE classification, enhancement of the type II IFN pathway allows for accumulation of autoantibodies and subsequent elevations in IFN-α activity immediately preceding SLE classification. Perturbations in select immunological processes may help identify at-risk individuals for further clinical evaluation or participation in prospective intervention trials.

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Heat-Etching with a Bullivant Type II Simple Freeze-Cleave Device

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100067522 ◽

1970 ◽

Vol 28 ◽

pp. 106-107 ◽

Cited By ~ 1

Author(s):

Ronald S. Weinstein ◽

N. Scott McNutt

Keyword(s):

New Zealand ◽

General Hospital ◽

Massachusetts General Hospital ◽

Type I ◽

Type Ii ◽

Collaborative Effort ◽

Temperature And Pressure ◽

The University

The Type I simple cold block device was described by Bullivant and Ames in 1966 and represented the product of the first successful effort to simplify the equipment required to do sophisticated freeze-cleave techniques. Bullivant, Weinstein and Someda described the Type II device which is a modification of the Type I device and was developed as a collaborative effort at the Massachusetts General Hospital and the University of Auckland, New Zealand. The modifications reduced specimen contamination and provided controlled specimen warming for heat-etching of fracture faces. We have now tested the Mass. General Hospital version of the Type II device (called the “Type II-MGH device”) on a wide variety of biological specimens and have established temperature and pressure curves for routine heat-etching with the device.

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Labelling of non-A, non-B hepatitis infected chimpanzee hepatocytes with nuclease-gold conjugates

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100111367 ◽

1984 ◽

Vol 42 ◽

pp. 250-251

Author(s):

G. D. Gagne ◽

M. F. Miller ◽

D. A. Peterson

Keyword(s):

Endoplasmic Reticulum ◽

Experimental Infection ◽

Uranyl Acetate ◽

Type I ◽

Cellular Injury ◽

Type Ii ◽

Tubular Structures ◽

Type Iii ◽

Type Iv ◽

Infected Chimpanzee

Experimental infection of chimpanzees with non-A, non-B hepatitis (NANB) or with delta agent hepatitis results in the appearance of characteristic cytoplasmic alterations in the hepatocytes. These alterations include spongelike inclusions (Type I), attached convoluted membranes (Type II), tubular structures (Type III), and microtubular aggregates (Type IV) (Fig. 1). Type I, II and III structures are, by association, believed to be derived from endoplasmic reticulum and may be morphogenetically related. Type IV structures are generally observed free in the cytoplasm but sometimes in the vicinity of type III structures. It is not known whether these structures are somehow involved in the replication and/or assembly of the putative NANB virus or whether they are simply nonspecific responses to cellular injury. When treated with uranyl acetate, type I, II and III structures stain intensely as if they might contain nucleic acids. If these structures do correspond to intermediates in the replication of a virus, one might expect them to contain DNA or RNA and the present study was undertaken to explore this possibility.

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Comparative surface and ultrastructural views of methylotrophic bacteria by TEM, STEM, SE, and freeze-etch electron microscopy.

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100128274 ◽

1987 ◽

Vol 45 ◽

pp. 792-793

Author(s):

T.A. Fassel ◽

M.J. Schaller ◽

M.E. Lidstrom ◽

C.C. Remsen

Keyword(s):

Cytoplasmic Membrane ◽

Structural Features ◽

Methylotrophic Bacteria ◽

Type I ◽

Type Ii ◽

Membrane Complex ◽

Oxidation Of Methane ◽

Methane Oxidizing Bacteria ◽

Wall Structures ◽

Methylomonas Albus

Methylotrophic bacteria play an Important role in the environment in the oxidation of methane and methanol. Extensive intracytoplasmic membranes (ICM) have been associated with the oxidation processes in methylotrophs and chemolithotrophic bacteria. Classification on the basis of ICM arrangement distinguishes 2 types of methylotrophs. Bundles or vesicular stacks of ICM located away from the cytoplasmic membrane and extending into the cytoplasm are present in Type I methylotrophs. In Type II methylotrophs, the ICM form pairs of peripheral membranes located parallel to the cytoplasmic membrane. Complex cell wall structures of tightly packed cup-shaped subunits have been described in strains of marine and freshwater phototrophic sulfur bacteria and several strains of methane oxidizing bacteria. We examined the ultrastructure of the methylotrophs with particular view of the ICM and surface structural features, between representatives of the Type I Methylomonas albus (BG8), and Type II Methylosinus trichosporium (OB-36).

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Emotion Regulation Difficulties in Survivors of Type I and Type II Traumas

PsycEXTRA Dataset ◽

10.1037/e517302011-169 ◽

2008 ◽

Author(s):

Thomas Ehring

Keyword(s):

Emotion Regulation ◽

Type I ◽

Type Ii

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Immortalized dendritic like cell lines derived from mice lacking both type I and type II interferon receptors, process and present MHC II restricted antigen to primed and naive T cells, induce MLR and support virus replication

Immunology Letters ◽

10.1016/s0165-2478(97)87906-0 ◽

1997 ◽

Vol 56 (1-3) ◽

pp. 267

Author(s):

R Nunez

Keyword(s):

T Cells ◽

Cell Lines ◽

Virus Replication ◽

Type I ◽

Type Ii ◽

Naive T Cells ◽

Naïve T Cells ◽

Mhc Ii

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OPTICAL STUDIES OF TYPE I AND TYPE II RECOMBINATION IN GaAs-AlAs QUANTUM WELLS

Le Journal de Physique Colloques ◽

10.1051/jphyscol:19875112 ◽

1987 ◽

Vol 48 (C5) ◽

pp. C5-525-C5-528 ◽

Cited By ~ 2

Author(s):

K. J. MOORE ◽

P. DAWSON ◽

C. T. FOXON

Keyword(s):

Quantum Wells ◽

Type I ◽

Type Ii ◽

Optical Studies

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An old friend is better than two new ones? Approaches to market research in the context of digital transformation for the antitrust laws enforcement

Voprosy Ekonomiki ◽

10.32609/0042-8736-2020-6-37-55 ◽

2020 ◽

pp. 37-55 ◽

Cited By ~ 1

Author(s):

A. E. Shastitko ◽

O. A. Markova

Keyword(s):

Business Models ◽

Rapid Development ◽

Digital Transformation ◽

Market Definition ◽

Type I ◽

Type Ii ◽

Digital Platforms ◽

Advantages And Disadvantages ◽

Pass Through ◽

Type Ii Errors

Digital transformation has led to changes in business models of traditional players in the existing markets. What is more, new entrants and new markets appeared, in particular platforms and multisided markets. The emergence and rapid development of platforms are caused primarily by the existence of so called indirect network externalities. Regarding to this, a question arises of whether the existing instruments of competition law enforcement and market analysis are still relevant when analyzing markets with digital platforms? This paper aims at discussing advantages and disadvantages of using various tools to define markets with platforms. In particular, we define the features of the SSNIP test when being applyed to markets with platforms. Furthermore, we analyze adjustment in tests for platform market definition in terms of possible type I and type II errors. All in all, it turns out that to reduce the likelihood of type I and type II errors while applying market definition technique to markets with platforms one should consider the type of platform analyzed: transaction platforms without pass-through and non-transaction matching platforms should be tackled as players in a multisided market, whereas non-transaction platforms should be analyzed as players in several interrelated markets. However, if the platform is allowed to adjust prices, there emerges additional challenge that the regulator and companies may manipulate the results of SSNIP test by applying different models of competition.

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Two Different UGT1A1 Mutations causing Crigler–Najjar Syndrome types I and II in an Iranian Family

Journal of Gastrointestinal and Liver Diseases ◽

10.15403/jgld.2014.1121.244.ugt ◽

2015 ◽

Vol 24 (4) ◽

pp. 523-526 ◽

Cited By ~ 1

Author(s):

Yoshihiro Maruo ◽

Mahdiyeh Behnam ◽

Shinichi Ikushiro ◽

Sayuri Nakahara ◽

Narges Nouri ◽

...

Keyword(s):

Serum Bilirubin ◽

Total Serum Bilirubin ◽

Total Serum ◽

Compound Heterozygous ◽

Type I ◽

Syndrome Type ◽

Type Ii ◽

Wild Type ◽

Iranian Family ◽

Udp Glucuronosyltransferase

Background: Crigler–Najjar syndrome type I (CN-1) and type II (CN-2) are rare hereditary unconjugated hyperbilirubinemia disorders. However, there have been no reports regarding the co-existence of CN-1 and CN-2 in one family. We experienced a case of an Iranian family that included members with either CN-1 or CN-2. Genetic analysis revealed a mutation in the bilirubin UDP-glucuronosyltransferase (UGT1A1) gene that resulted in residual enzymatic activity.Case report: The female proband developed severe hyperbilirubinemia [total serum bilirubin concentration (TB) = 34.8 mg/dL] with bilirubin encephalopathy (kernicterus) and died after liver transplantation. Her family history included a cousin with kernicterus (TB = 30.0 mg/dL) diagnosed as CN-1. Her great grandfather (TB unknown) and uncle (TB = 23.0 mg/dL) developed jaundice, but without any treatment, they remained healthy as CN-2. Results: The affected cousin was homozygous for a novel frameshift mutation (c.381insGG, p.C127WfsX23). The affected uncle was compound heterozygous for p.C127WfsX23 and p.V225G linked with A(TA)7TAA. p.V225G-UGT1A1 reduced glucuronidation activity to 60% of wild-type. Thus, linkage of A(TA)7TAA and p.V225G might reduce UGT1A1 activity to 18%–36 % of the wild-type. Conclusion: Genetic and in vitro expression analyses are useful for accurate genetic counseling for a family with a history of both CN-1 and CN-2. Abbreviations: CN-1: Crigler–Najjar syndrome type I; CN-2: Crigler–Najjar syndrome type II; GS: Gilbert syndrome; UGT1A1: bilirubin UDP-glucuronosyltransferase; WT: Wild type; TB: total serum bilirubin.

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