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A Celebration Of Faculty Scholarship - 2016, Dean's Office, College Of The Holy Cross

Annual Bibliography of Faculty Publications

A listing of the scholarly and creative work produced by the faculty of the College of the Holy Cross. It includes articles, book chapters, productions, exhibitions, grants and reviews reported for the 2015-2016 academic year.

Spartan Daily, May 10, 2016, San Jose State University, School Of Journalism And Mass Communications

Spartan Daily, 2016

Volume 146, Issue 40

Reduction Of N-Glycan Profile Variation By Using Capacitance Probes For Optimized Process Control, Christopher Bro, Tom Kristensen, Michael Wahlers, An Zhang, Anne Tollstrup

Cell Culture Engineering XV

The glycan profile of therapeutic monoclonal antibodies frequently plays an important role in their biological function and pharmacokinetics. Therefore, improved control of the glycosylation profile of biopharmaceutical monoclonal antibodies has become an increased priority during late stage and commercial manufacturing of New Biological Entities as well as biosimilars. Two ways to obtain better control are through process parameter optimization and/or through addition of media supplements to the production reactor. Cell culture supplementation with mycophenolic acid is one method to efficiently manipulate N-glycan profiles of monoclonal antibodies, notably the level of fucosylation. We have observed at least for some CHO-based cell …

Impact Of Culture Conditions And Cell Age On Sequence Variant Levels In Monoclonal Antibody Biotherapeutics, Karin Anderson

Cell Culture Engineering XV

Sequence variants (SV) are protein products that contain unintended substitutions in the amino acid sequence. SV are one source of heterogeneity inherent to biological systems. They can arise from multiple sources within CHO cells including mutations in genomic DNA, transcription and/or translation errors, splice variants, and post translational modifications. This poster focuses on SV resulting from single base changes in a copy of the integrated exogenous gene in genomic DNA of single cell cloned CHO cell lines.

The increased sensitivity and selectivity of analytical instruments and methods has revealed across industry that a number of cloned CHO cell lines, including …

Scale-Up And Scale-Down Challenges For A High Density Long-Term Perfusion Suspension Cell Culture In Large-Scale Single Use Bioreactors, Weichang Zhou, Hang Zhou

Cell Culture Engineering XV

As part of efforts to develop a continuous processing platform for biologics manufacturing using single use bioreactors, we have been focusing on development of several initial unit operations: high density perfusion suspension cell cultures and early product capture steps, in order to realize its potentials of being flexible, improving product quality and lowering costs. These initial unit operations require large volumes and represent the most important part of this processing platform. By integrating these steps into a continuous operation, we can deliver the largest benefits of this processing platform. In this presentation, we will discuss our efforts towards continuous biologics …

Changes In Product Quality – What Is Comparable “Enough” And What Is “Similar Enough?”, David Robinson

Cell Culture Engineering XV

Regulatory guidance documents clearly outline the requirements for demonstrating analytical comparability to support process changes and analytical similarity to support the approval of biosimilars. These include demonstration that process changes do not produce differences in product characteristics that might lead to an adverse impact on the safety or efficacy of the product¹. For biosimilar products, a stepwise approach is required that starts with sponsors demonstrating that the product characteristics of the proposed biosimilar are either highly similar to that of the originator reference product or that any observed differences can be demonstrated to not impact the ability to …

Demonstrating Process Performance Comparability Of The Keytruda® Upstream Process After Transfer And Scale-Up To Different Manufacturing Sites, Jurgen Van De Lagermaat

Cell Culture Engineering XV

The Keytruda® drug substance manufacturing process was transferred and scaled up from a donor manufacturing site (12,500 L bioreactor WV) to two additional recipient sites (12,000 L and 22,000 L bioreactor WV) to further expand drug substance production capacity of Merck’s novel monoclonal antibody against PD-1. Process facility fit into the recipient manufacturing facilities was required due to differences in equipment and operation as compared to the donor site and therefore upstream process performance comparability needed to be demonstrated (regulatory requirement). A three-level comparability approach was used, whereby upstream intermediate product quality (Level 1), cell culture performance KPAs (Level 2) …

Critical Process Parameter Identification Using The Ambr15(Tm) For Process Characterization, Matthew Zustiak, Michael Bennett, Stephanie Chakravarty, Matt Caple

Cell Culture Engineering XV

Process characterization is a critical phase in the development of a commercial process for biotherapeutic production. Knowing the critical quality attributes of your molecule prior to beginning process development and/or characterization is imperative when using a quality by design (QbD) approach. Here we use a (QbD) approach for the characterization of a fed-batch process using an NSO cell line to express an IgG. For this molecule, the glycosylation profile, and in particular, the total fucosylation was identified as a critical quality attribute. After performing a primary hazard analysis, several process inputs were determined to potentially have an impact on this …

Methods For Treating Papilloma Virus Infection, James K. Bashkin, Terri G. Edwards, Christopher Fisher, Kevin J. Koeller

UMSL Patents

For the most up-to-date information about these patents, including the availability of Certificates of Correction, be sure to check the United States Patent and Trademark Office's free, publicly accessible database: Patent Public Search https://ppubs.uspto.gov/pubwebapp/static/pages/landing.html

Enhancing Enveloped Viral Particles Production By Targeted Supplementation Design: Releasing Bottlenecks In Ic-Bevs, Francisca Monteiro

Cell Culture Engineering XV

The increasing demand of Insect Cell-Baculovirus Expression Vector System (IC-BEVS) based biopharmaceuticals raises the interest in developing high-titer production processes. Previously, we addressed the impact of the baculovirus infection on the physiology of High Five and Sf9 host cell lines, stressing out key cellular features that support higher productivities. This information was applied to design tailored supplementation schemes to boost IC-BEVS production yields of three targets with increasing complexity: recombinant influenza neuraminidase (rNeur); enveloped influenza VLPs (Inf-VLP) and the baculovirus itself (BV). Higher rNeur productivities were achieved when supplementing High Five cultures with cholesterol. For Sf9 cells, GSH, antioxidants combined …

A Stochastic Model To Study Genetic And Metabolic Effects On N-Linked Protein Glycosylation, Phillip Spahn, Anders Hansen, Henning Hansen, Johnny Arnsdorf, Helene Kildegaard, Nathan Lewis

Cell Culture Engineering XV

Glycosylation is a vital processing step for a large number of cellular proteins as it critically affects protein stability and solubility as well as protein-protein interactions. As a consequence, glycosylation is a major quality attribute of recombinant proteins in biopharmaceutical applications. However, since glycosylation does not follow a template, but instead involves a complex interplay of various influencing factors in the Golgi, tailoring glycosylation towards certain desired attributes is challenging and usually requires trial-and-error experimentation. Computational modeling offers an intriguing option to understand and rationally engineer the complex reaction network underlying glycosylation. Here we present a computational model that describes …

Life In The Fast Lane: Developing And Commercializing Keytruda®, A Novel Breakthrough Therapy Designation Oncology Therapy, In Three Years From First Patient Dosed To Us Approval, Gargi Maheshwaru, Athena Nagi, Ronald Smulders, Fergal O´Donovan, Kimberly May, Tamas Blandi, Marc Bastiaansen

Cell Culture Engineering XV

In order to accelerate the availability of novel potentially life-saving therapies, the FDA has developed multiple programs, including recently assigning breakthrough therapy designation to promising candidates in development. At the time of breakthrough therapy designation, Merck had only manufactured supplies at a small clinical scale facility. In order to meet forecasts for projected commercial and clinical demand and to ensure uninterrupted supply for Keytruda®, a novel monoclonal

antibody against PD-1, Merck commercialized two drug substance facilities in parallel. Through multiple interactions with the FDA, both facilities were licensed, one that was the initial clinical supply site, and, a …

05/10/2016 Obituary Records, Hawaii Obituaries

Obituaries

List of Obituaries for individuals who passed away on 05/10/2016. Scroll down to see the names and obituary description.

Not Yet Legal And In Prison?, Araseli Saldivar

Themis: Research Journal of Justice Studies and Forensic Science

The United States is the only industrialized country that

sentences individuals to spend the remainder of their lives in

prison for a crime they committed before the age of eighteen.

The justice system established the sentencing of juveniles to life

in prison without the possibility of parole to deter juvenile

delinquency. Life without parole was regarded as an appropriate

punishment following the rise of juvenile crime during the 1980s

and 1990s. However, as psychological differences between

juveniles and adults became more prominent, society began to

regard life without the possibility of parole as a cruel and

unusual punishment. Although some …

Threatened And Invasive Reptiles Are Not Two Sides Of The Same Coin, Reid Tingley, Peter J. Mahoney, Andrew M. Durso, Aimee G. Tallian, Alejandra Moran-Ordonez, Karen H. Beard

Wildland Resources Faculty Publications

The ‘two sides of the same coin’ hypothesis posits that biological traits that predispose species to extinction and invasion lie on opposite ends of a continuum. Conversely, anthropogenic factors may have similar effects on extinction and invasion risk. We test these two hypotheses using data on more than 1000 reptile species.

A Prison Of Education: The School-To-Prison Pipeline In Low-Income Schools, Adam Le

Themis: Research Journal of Justice Studies and Forensic Science

This paper examines the relationship between prisons and education in American culture, comparing public schools in California cities to wealthier private schools. The essay critiques the American dream’s notions of social stratification and success of the individual in racialized areas. The first section compares funding disparities between education and prison and argues that while funding is an integral part of the inner-city’s problem, the curriculum itself is ineffective. The second section takes a closer look at differences in the curricula and educational settings of an inner-city school and a private school. It offers ethnic studies in secondary education as a …

The Thirteenth Amendment, Disparate Impact, And Empathy Deficits, Darrell A.H. Miller

Seattle University Law Review

Modern civil rights policy is, as the late Justice Scalia warned, at “war.” On the one hand, some laws, like Title VII of the Civil Rights Act of 1964 (Title VII) and the Fair Housing Act, can impose liability for decisions due to their racial impacts rather than their racial motivation. Defendants in such cases can always respond that the challenged decision (a test, a criterion, an allocation) is necessary in some legally cognizable sense; but the courthouse doors open with the prima facie case of disparate impact. On the other hand, the Fourteenth Amendment’s Equal Protection Clause, ever since …

An Assessment Of The Use Hand, Digital And Hybrid Graphics In Contemporary Landscape Architecture Practice, Natalia Chuprakova

Landscape Architecture Masters & Design Theses - Archive

Visual representation is a critical component of professional landscape architecture practice. The tools that are used for visual representation production are hand, digital and hybrid graphics. This thesis evaluates the existing representational tools available in professional practice within United States. It takes into consideration factors such as professional position, years of accrued experience in the profession, level of professional degree and type of landscape architecture practice and shows how the various factors noted above influence choices made regarding graphics type preference. Furthermore, this study evaluates the role that given graphics types play in the design process, as well as current …

After 30 Years At Uab, Vp Marchase Announces Plans To Retire, Jim Bakken

Browse All News

No abstract provided.

Franklin Delano Roosevelt: The Diagnosis Of Poliomyelitis Revisited., John F. Ditunno, Jr, Bruce E. Becker, Gerald J. Herbison

Department of Rehabilitation Medicine Faculty Papers

Revisiting the ailments of famous historical persons in light of contemporary medical understanding has become a common academic hobby. Public discussion of Franklin Delano Roosevelt's (FDR) diagnosis of poliomyelitis after his sudden onset of paralysis in 1921 has received just such a revisitation. Recently, this 2003 historical analysis has been referenced widely on the Internet and in biographies, raising speculation that his actual diagnosis should have been Guillain-Barré Syndrome, a noncontagious disease of the peripheral nervous system rather than poliomyelitis. The authors of that 2003 analysis used a statistical analysis of his case by selectively choosing some of his reported …

The Thirteenth Amendment At The Intersection Of Class And Gender: Robertson V. Baldwin’S Exclusion Of Infants, Lunatics, Women, And Seamen, James Gray Pope

Seattle University Law Review

In Robertson v. Baldwin, the Supreme Court held that merchant seamen under contract could be legally compelled to work notwithstanding the Thirteenth Amendment’s prohibition on slavery and involuntary servitude. According to the Court, seamen were “deficient in that full and intelligent responsibility for their acts which is accredited to ordinary adults,” and therefore could—along with children and wards—be deprived of liberty. Over the past few years, however, several courts have applied statutory bans on “involuntary servitude” and “forced labor” (a “species of involuntary servitude”) to protect women and children in domestic settings. These cases suggest that Robertson’s categorical exclusion is …

An Overture To Equality: Preventing Subconscious Sex And Gender Biases From Influencing Hiring Decisions, Christy Krawietz

Seattle University Law Review

In many industries, women are less likely than men to be hired, and research suggests that this is due to subconscious gender bias rather than meritorious difference. To combat this bias, some orchestras use gender-blind auditions to hire their musicians. Orchestral hopefuls sit behind a screen to play their pieces, and directors listen to determine whom they want to hire. Some orchestras require applicants to remove their shoes before walking onstage, as even the perceived sound of high heels can affect a director’s decision. Before instituting gender-blind auditions, the top five American orchestras had fewer than five percent women players. …

Bioreactor Perfusion Via Single-Use Centrifugation Has Fewer Product Quality Implications Than Tangential Flow Filtration, Rustin Shenkman, Douglas Gunzelmann, Ting Yang, Matthew Traylor, Kenneth Manning

Cell Culture Engineering XV

During development of a perfusion cell culture process for the production of a therapeutic protein, tangential flow filtration (TFF) technology was evaluated for cell retention in addition to Shire’s platform single-use centrifugation technology. Unlike centrifugation TFF is based on a microfiltration membrane and thus has the potential to partially retain many biological compounds, especially when exposed to extracellular matrix proteins and antifoam emulsions (Routledge, 2012; Wu et al., 2011). Retention increases the mean residence time of product at process temperature. In the case of heat-labile molecules longer exposure to bioreactor culture temperature may correlate with changes in quality attributes.

Therapeutic …

The Foundations Of Network Dynamics In An Rna Recombinase System, Jessica Anne Mellor Yeates

Dissertations and Theses

How life originated from physical and chemical processes is one of the great questions still unanswered today. Studies towards this effort have transitioned from the notion of a single self-replicating entity to the idea that a network of interacting molecules made this initial biological leap. In order to understand the chemical kinetic and thermodynamic mechanisms that could engender pre-life type networks we present an empirical characterization of a network of RNA recombinase molecules. We begin with 1-, 2-, and 3-molecular ensembles and provide a game theoretic analysis to describe the frequency dependent dynamics of competing and cooperating RNA genotypes. This …

Aligning Citylab Biotechnology Curriculum With Ngss Standards And Practices, Arianna Jefferson

Honors Program Theses and Projects

No abstract provided.

Physiological And Behavioral Effects Of High Fat Diet Removal And Wheel Running In C57bl/6j Mice, Aikaterini Hatzidis

Honors Program Theses and Projects

The possibility of developing Type 2 Diabetes Mellitus (T2DM) is determined by a combination of genetic factors and the lifestyle of the individual. Higher risks of T2DM diagnosis occur when individuals are exposed to lifestyle factors such as physical inactivity and high fat diet consumption. Animal models, including mice, are consistently used in laboratory studies to understand T2DM in humans due to genetic and physiological similarities. This study focuses on whether change of diet and increased exercise can reduce obesity and alleviate T2DM symptoms in C57BL/6J (B6) mice. Changes in weight, anxiety-like behaviors, leptin and insulin levels and glucose tolerance …

An Examination Of Gene Wolfe's The Book Of The New Sun: Literary And Mythological Significance, Tyler Garvey

Honors Program Theses and Projects

No abstract provided.

Replacing Arginine 33 For Alanine In The Hemophore Hasa From Pseudomonas Aeruginosa Causes Closure Of The H32 Loop In The Apo-Protein, Ritesh Kumar, Yifei Qi, Hirotoshi Matsumura, Scott Lovell, Huili Yao, Kevin P. Battaile, Wonpil Im, Pierre Moënne-Loccoz, Mario Rivera

Faculty Publications

© 2016 American Chemical Society. Previous characterization of hemophores from Serratia marcescens (HasAs), Pseudomonas aeruginosa (HasAp), and Yersinia pestis (HasAyp) showed that hemin binds between two loops, where it is axially coordinated by H32 and Y75. The Y75 loop is structurally conserved in all three hemophores and harbors conserved ligand Y75. The other loop contains H32 in HasAs and HasAp, but a noncoordinating Q32 in HasAyp. The H32 loop in apo-HasAs and apo-HasAp is in an open conformation, which places H32 about 30 Å from the hemin-binding site. Hence, hemin binding onto the Y75 loop of HasAs or HasAp triggers …

Genetic Relationship Between Schizophrenia And Nicotine Dependence, J Chen, S A. Bacanu, H Yu, Z Zhao, P Jia, K S. Kendler, H R. Kranzler, J Gelernter, L Farrer, C Minica, R Pool, Y Milaneschi, D I. Boomsma, B Wjh Penninx, R F. Tyndale, J J. Ware, J M. Vink, J Kaprio, M Munafò, X Chen

Physics & Astronomy Faculty Research

It is well known that most schizophrenia patients smoke cigarettes. There are different hypotheses postulating the underlying mechanisms of this comorbidity. We used summary statistics from large meta-analyses of plasma cotinine concentration (COT), Fagerström test for nicotine dependence (FTND) and schizophrenia to examine the genetic relationship between these traits. We found that schizophrenia risk scores calculated at P-value thresholds of 5 × 10-3 and larger predicted FTND and cigarettes smoked per day (CPD), suggesting that genes most significantly associated with schizophrenia were not associated with FTND/CPD, consistent with the self-medication hypothesis. The COT risk scores predicted schizophrenia diagnosis at P-values …

Division Of Labour: A Democratic Approach Towards Understanding Manual Asymmetries In Non-Human Primates, Madhur Mangalam, Nisarg Desai, Mewa Singh

Journal Articles

A consequence of the 'gold rush'-like hunch for human-like handedness in non-human primates has been that researchers have been continually analysing observations at the level of the population, ignoring the analysis at the level of an individual and, consequently, have potentially missed revelations on the forms and functions of manual asymmetries. Recently, consecutive studies on manual asymmetries in bonnet macaques, Macaca radiata revealed both the functional and adaptive significance of manual asymmetries respectively, and pointed towards the division of labour as being the general principle underlying the observed hand-usage patterns. We review the studies on manual asymmetries in capuchin monkeys, …