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The recent clinical and commercial success of lipid nanoparticles (LNPs) for nucleic acid delivery has incentivized the development of new technologies to manufacture LNPs. As new technologies emerge, researchers must determine which technologies to assess and how to perform comparative evaluations. In this article, we use a quality-by-design approach to systematically investigate how the mixer technology used to form LNPs influences LNPstructure. Specifically, a coaxial turbulent jet mixer and a staggered herringbone microfluidic mixer were systematically compared via matched formulation and process conditions. A full-factorial design-of-experiments study with three factors and three levels was executed for each mixer to compare process robustness in the production of antisense oligonucleotide (ASO) LNPs. ASO-LNPs generated with the coaxial turbulent jet mixer were consistently smaller, had a narrower particle size distribution, and had a higher ASO encapsulation as compared to the microfluidic mixer, but had a greater variation in internal structure with less ordered cores. A subset of the study was replicated for mRNA-LNPs with comparable trends in particle size and encapsulation, but more frequent bleb features for LNPs produced by the coaxial turbulent jet mixer. The study design used here provides a road map for how researchers may compare different mixer technologies (or process changes more broadly) and how such studies can inform process robustness and manufacturing control strategies.

AIMS: To evaluate if a deep learning algorithm can be trained to identify tumour-infiltrating lymphocytes (TILs) in tissue samples of testicular germ cell tumours and to assess whether the TIL counts correlate with relapse status of the patient. METHODS: TILs were manually annotated in 259 tumour regions from 28 whole-slide images (WSIs) of H&E-stained tissue samples. A deep learning algorithm was trained on half of the regions and tested on the other half. The algorithm was further applied to larger areas of tumour WSIs from 89 patients and correlated with clinicopathological data. RESULTS: A correlation coefficient of 0.89 was achieved when comparing the algorithm with the manual TIL count in the test set of images in which TILs were present (n=47). In the WSI regions from the 89 patient samples, the median TIL density was 1009/mm2. In seminomas, none of the relapsed patients belonged to the highest TIL density tertile (>2011/mm2). TIL quantifications performed visually by three pathologists on the same tumours were not significantly associated with outcome. The average interobserver agreement between the pathologists when assigning a patient into TIL tertiles was 0.32 (Kappa test) compared with 0.35 between the algorithm and the experts, respectively. A higher TIL density was associated with a lower clinical tumour stage, seminoma histology and lack of lymphovascular invasion. CONCLUSIONS: Deep learning-based image analysis can be used for detecting TILs in testicular germ cell cancer more objectively and it has potential for use as a prognostic marker for disease relapse.

Greenish-gray (C155) cloth; black, white and orange pictorial panel of fighting sailors, white lettering; black sword and wreath, white lettering on spine; pictorial endpapers printed in green, "J J R", possibly Joseph Johnson Ray. H: 19 cm.; W: 12.5 cm.; D: 3.5 cm.

Petition to add or replace a Justice of the Peace due to change in county lines.

Program of The Karamu Dancers in Concert. This performance ran from May 16-25, 1968. Performers: Pearl Johnson, Kathryn Karipides, Leslie Woideck, Eugenia Love, Thomas Hartshorne, Carolyn Coles, James Nicholson, Joseph Berkins, Roger Mae Johnson, Pam Schick, and Mami Johnson.

Program of The Karamu Dancers in Concert. This performance ran from May 27-June 6, 1964. Performers: Joseph Berkins, June Moxley, Jacqueline Earley, Leonore Spinell, William Wingfield, Emmanuel Sauls, Benjamin Turner, James Nicholson, Kathy Karipedes, Jean Love, Joan Hartshorne, Pearl Johnson, Joseph Berkins, Roger Johnson, Michael Luck, Timatha McGoff, and Christine Buster.

Theater program of "Hoboken Blues, or Rip Van Winkle, Black" by Michael Gold. This performance ran from November 21-25, 1934. Performers: William Williams as Chill McGregor, Festus Fitzhugh as Henry, Hazel Walker as Amelia, Leslie Ingram as Conductor of the Horse Car, Joseph Singleton as Little Joe McGregor, William Johnson as Sam Pickens, Louise Apple as Sally Pickens, Sherman Brown as Barney, Percy Marshall as Jeff Adams, George Vilkinson as Kid Mumbo, Olive Hale as Granny Pickens, Joseph King as Policeman, Paul Banks as Rev. Rosewater, Fitzhugh Woodford as Undertaker Butler, Donald Moore as Oswald Butler, Leslie Ingram as Daddy Jake, Mamie Bowdry as Honey Lou Pickens, Brownie Woodford as The Lady in the Cafe, David Beasley as The Gentleman in the Cafe, Leslie Ingram as The Head Waiter, George Guinn as The Stock Broker, William Williams as The Bum, William Day/George Wilkinson as The Clowns, Fitzhugh Woodford as The Ringmaster, Festus Fitzhugh as The Savage, Percy Marshall, George Guinn, Jack Stewart, and Sherman Brown as the Policemen, Hazel Walker as The Mayor, Paul Banks as The Preacher, Brownie Woodford as Women's Club President, William Williams as Christopher Columbus, Elmer Cheeks as George Washington, Olive Hale as The Old African Woman, Louise Apple as Brown Skin Angel, Hazel Walker as The Judge, Fitzhugh Woodford as The Capitalist, Jesse Firse as Plato, Joseph King as Spartacus, and Leslie Ingram as Fordist.