Digital transformation in bio manufacturing

This presentation describes ways to leverage and implement digitalization technologies in biopharmaceutical manufacturing. An accelerated process development workflow is described that employs micro-scale technologies, modular unit operations with integrated process control and monitoring systems, systems integration, and full plant automation. The presentation describes how to best develop and transfer knowledge between steps in the workflow via first-principles models, data analytics, and machine learning. Case studies are described that illustrate the application of each of the above methods, including where process equipment was designed digitally by using first-principles models first, then the process equipment was constructed and implemented experimentally, with the experimental results confirming model predictions

Plug-and-play software for mechanistic modelling of end-to-end continuous manufacturing of monoclonal antibodies

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Extension for Community Healthcare Outcomes-Palliative Care in Africa Program: Improving Access to Quality Palliative Care

Purpose: There is limited access to quality palliative care (PC) for patients with advanced cancer in sub-Saharan Africa. Our aim was to describe the development of the Project Extension for Community Healthcare Outcomes- Palliative Care in Africa (ECHO-PACA) program and describe a preliminary evaluation of attitudes and knowledge of participants regarding the ability of the program to deliver quality PC. Methods: An interdisciplinary team at the MD Anderson Cancer Center, guided by experts in PC in sub-Saharan Africa, adapted a standardized curriculum based on PC needs in the region. Participants were then recruited, and monthly telementoring sessions were held for 16 months. The monthly telementoring sessions consisted of case presentations, discussions, and didactic lectures. Program participants came from 14 clinics and teaching hospitals in Ghana, Kenya, Nigeria, South Africa, and Zambia. Participants were surveyed at the beginning, midpoint, and end of the 16-month program to evaluate changes in attitudes and knowledge of PC. Results: The median number of participants per session was 30. Thirty-three (83%) of 40 initial participants completed the feedback survey. Health care providers’ self-reported confidence in providing PC increased with participation in the Project ECHO-PACA clinic. There was significant improvement in the participants’ attitudes and knowledge, especially in titrating opioids for pain control (P = .042), appropriate use of non-opioid analgesics (P = .012), and identifying and addressing communication issues related to end-of-life care (P = .014). Conclusion: Project ECHO-PACA was a successful approach for disseminating knowledge about PC. The participants were adherent to ECHO PACA clinics and the completion of feedback surveys. Future studies should evaluate the impact of Project ECHO-PACA on changes in provider practice as well as patient outcomes

Novel genetic variants of PIP5K1C and MVB12B of the endosome-related pathway predict cutaneous melanoma-specific survival

Endosomes regulate cell polarity, adhesion, signaling, immunity, and tumor progression, which may influence cancer outcomes. Here we evaluated associations between 36,068 genetic variants of 228 endosome-related pathway genes and cutaneous melanoma disease-specific survival (CMSS) using genotyping data from two previously published genome-wide association studies. The discovery dataset included 858 CM patients with 95 deaths from The University of Texas MD Anderson Cancer Center, and the replication dataset included 409 CM patients with 48 deaths from the Nurses’ Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). In multivariate Cox proportional hazards regression analysis, we found that two novel SNPs (PIP5K1C rs11666894 A>C and MVB12B rs12376285 C>T) predicted CMSS, with adjusted hazards ratios of 1.47 (95% confidence interval = 1.15-1.89 and P = 0.002) and 1.73 (1.30-2.31 and 0.0002), respectively. Combined analysis of risk genotypes of these two SNPs revealed a dose-dependent decrease in CMSS associated with an increased number of risk genotypes (P trend = 0.0002). Subsequent expression quantitative trait loci (eQTL) analysis revealed that PIP5K1C rs11666894 was associated with mRNA expression levels in lymphoblastoid cell lines from 373 European descendants (P<0.0001) and that MVB12B rs12376285 was associated with mRNA expression levels in cultured fibroblasts from 605 European-Americans (P<0.0001). Our findings suggest that novel genetic variants of PIP5K1C and MVB12B in the endosome-related pathway genes may be promising prognostic biomarkers for CMSS, but these results need to be validated in future larger studies

Biomanufacturing and testbed development for the continuous production of monoclonal antibodies

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Probing BFKL Dynamics in the Dijet Cross Section at Large Rapidity Intervals in ppbar Collisions at sqrt{s}=1800 and 630 GeV

Inclusive dijet production at large pseudorapidity intervals (delta_eta) between the two jets has been suggested as a regime for observing BFKL dynamics. We have measured the dijet cross section for large delta_eta in ppbar collisions at sqrt{s}=1800 and 630 GeV using the DO detector. The partonic cross section increases strongly with the size of delta_eta. The observed growth is even stronger than expected on the basis of BFKL resummation in the leading logarithmic approximation. The growth of the partonic cross section can be accommodated with an effective BFKL intercept of a_{BFKL}(20GeV)=1.65+/-0.07.Comment: Published in Physical Review Letter

Search for Second Generation Leptoquark Pairs in pbar-p Collisions at sqrt(s) = 1.8 TeV

We have searched for second generation leptoquark (LQ) pairs in the \mu\mu+jets channel using 94+-5 pb^{-1} of pbar-p collider data collected by the D0 experiment at the Fermilab Tevatron during 1993-1996. No evidence for a signal is observed. These results are combined with those from the \mu\nu+jets and \nu\nu+jets channels to obtain 95% confidence level (C.L.) upper limits on the LQ pair production cross section as a function of mass and $beta, the branching fraction of a LQ decay into a charged lepton and a quark. Lower limits of 200(180) GeV/c^2 for \beta=1(1/2) are set at the 95% C.L. on the mass of scalar LQ. Mass limits are also set on vector leptoquarks as a function of \beta.Comment: 6 pages, 4 figures. Submitted to Phys. Rev. Let

Spin Correlation in tt-bar Production from pp-bar Collisions at sqrt(s)=1.8 TeV

The D0 collaboration has performed a study of spin correlation in tt-bar production for the process tt-bar to bb-bar W^+W^-, where the W bosons decay to e-nu or mu-nu. A sample of six events was collected during an exposure of the D0 detector to an integrated luminosity of approximately 125 pb^-1 of sqrt{s}=1.8 TeV pp-bar collisions. The standard model (SM) predicts that the short lifetime of the top quark ensures the transmission of any spin information at production to the tt-bar decay products. The degree of spin correlation is characterized by a correlation coefficient k. We find that k>-0.25 at the 68% confidence level, in agreement with the SM prediction of k=0.88.Comment: Submitted to PRL, Added references, minor changes to tex

Differential Production Cross Section of Z Bosons as a Function of Transverse Momentum at sqrt{s}=1.8 TeV

We present a measurement of the transverse momentum distribution of Z bosons produced in ppbar collisions at sqrt{s}=1.8 TeV using data collected by the D0 experiment at the Fermilab Tevatron Collider during 1994--1996. We find good agreement between our data and a current resummation calculation. We also use our data to extract values of the non-perturbative parameters for a particular version of the resummation formalism, obtaining significantly more precise values than previous determinations.Comment: 10 pages, 2 figures, submitted to Phys. Rev. Letters v2 has margin error correcte

A measurement of the W boson mass using large rapidity electrons

We present a measurement of the W boson mass using data collected by the D0 experiment at the Fermilab Tevatron during 1994--1995. We identify W bosons by their decays to e-nu final states where the electron is detected in a forward calorimeter. We extract the W boson mass, Mw, by fitting the transverse mass and transverse electron and neutrino momentum spectra from a sample of 11,089 W -> e nu decay candidates. We use a sample of 1,687 dielectron events, mostly due to Z -> ee decays, to constrain our model of the detector response. Using the forward calorimeter data, we measure Mw = 80.691 +- 0.227 GeV. Combining the forward calorimeter measurements with our previously published central calorimeter results, we obtain Mw = 80.482 +- 0.091 GeV