The contractor responsible for providing food to over 200 students has claimed to have purchased the pickle from outside

[London] : Published for the Royal Society of Literature by Geoffrey Cumberlege Oxford University Press, London, New York, Toronto, 1953.

PAGO PAGO, American Samoa - Today, the U.S. Environmental Protection Agency (EPA) announced that American Samoa was selected to receive a $300,000 grant to assess and clean up contaminated properties under the agency’s Brownfields Program.

Deaths and hospitalizations related to COVID-19 could increase dramatically in Montreal if social distancing measures are lifted, according to a new study.

7 October 2014

Antibodies are widely used as cancer therapeutics, but their current use is limited by the low number of antigens restricted to cancer cells. A receptor tyrosine kinase, receptor tyrosine kinase-like orphan receptor 2 (ROR2), is normally expressed only during embryogenesis and is tightly down-regulated in postnatal healthy tissues. However, it is up-regulated in a diverse set of hematologic and solid malignancies, thus ROR2 represents a candidate antigen for antibody-based cancer therapy. Here we describe the affinity maturation and humanization of a rabbit mAb that binds human and mouse ROR2 but not human ROR1 or other human cell-surface antigens. Co-crystallization of the parental rabbit mAb in complex with the human ROR2 kringle domain (hROR2-Kr) guided affinity maturation by heavy-chain complementarity-determining region 3 (HCDR3)-focused mutagenesis and selection. The affinity-matured rabbit mAb was then humanized by complementarity-determining region (CDR) grafting and framework fine tuning and again co-crystallized with hROR2-Kr. We show that the affinity-matured and humanized mAb retains strong affinity and specificity to ROR2 and, following conversion to a T cell–engaging bispecific antibody, has potent cytotoxicity toward ROR2-expressing cells. We anticipate that this humanized affinity-matured mAb will find application for antibody-based cancer therapy of ROR2-expressing neoplasms.

Prevention of aberrant cutaneous wound repair and appropriate regeneration of an intact and functional integument require the coordinated timing of fibroblast and keratinocyte migration. Here, we identified a mechanism whereby opposing cell-specific motogenic functions of a multifunctional intracellular and extracellular protein, the receptor for hyaluronan-mediated motility (RHAMM), coordinates fibroblast and keratinocyte migration speed and ensures appropriate timing of excisional wound closure. We found that, unlike in WT mice, in Rhamm-null mice, keratinocyte migration initiates prematurely in the excisional wounds, resulting in wounds that have re-surfaced before the formation of normal granulation tissue, leading to a defective epidermal architecture. We also noted aberrant keratinocyte and fibroblast migration in the Rhamm-null mice, indicating that RHAMM suppresses keratinocyte motility but increases fibroblast motility. This cell context–dependent effect resulted from cell-specific regulation of extracellular signal-regulated kinase 1/2 (ERK1/2) activation and expression of a RHAMM target gene encoding matrix metalloprotease 9 (MMP-9). In fibroblasts, RHAMM promoted ERK1/2 activation and MMP-9 expression, whereas in keratinocytes, RHAMM suppressed these activities. In keratinocytes, loss of RHAMM function or expression promoted epidermal growth factor receptor–regulated MMP-9 expression via ERK1/2, which resulted in cleavage of the ectodomain of the RHAMM partner protein CD44 and thereby increased keratinocyte motility. These results identify RHAMM as a key factor that integrates the timing of wound repair by controlling cell migration.

Inter-α-inhibitor is a proteoglycan essential for mammalian reproduction and also plays a less well-characterized role in inflammation. It comprises two homologous “heavy chains” (HC1 and HC2) covalently attached to chondroitin sulfate on the bikunin core protein. Before ovulation, HCs are transferred onto the polysaccharide hyaluronan (HA) to form covalent HC·HA complexes, thereby stabilizing an extracellular matrix around the oocyte required for fertilization. Additionally, such complexes form during inflammatory processes and mediate leukocyte adhesion in the synovial fluids of arthritis patients and protect against sepsis. Here using X-ray crystallography, we show that human HC1 has a structure similar to integrin β-chains, with a von Willebrand factor A domain containing a functional metal ion-dependent adhesion site (MIDAS) and an associated hybrid domain. A comparison of the WT protein and a variant with an impaired MIDAS (but otherwise structurally identical) by small-angle X-ray scattering and analytical ultracentrifugation revealed that HC1 self-associates in a cation-dependent manner, providing a mechanism for HC·HA cross-linking and matrix stabilization. Surprisingly, unlike integrins, HC1 interacted with RGD-containing ligands, such as fibronectin, vitronectin, and the latency-associated peptides of transforming growth factor β, in a MIDAS/cation-independent manner. However, HC1 utilizes its MIDAS motif to bind to and inhibit the cleavage of complement C3, and small-angle X-ray scattering–based modeling indicates that this occurs through the inhibition of the alternative pathway C3 convertase. These findings provide detailed structural and functional insights into HC1 as a regulator of innate immunity and further elucidate the role of HC·HA complexes in inflammation and ovulation.

Public Policy Institute of California researchers Magnus Lofstrom and Laura Hill discuss their research examining the potential labor market outcomes and other possible economic effects of a legalization program.

Public Policy Institute of California researchers Magnus Lofstrom and Laura Hill discuss their research examining the potential labor market outcomes and other possible economic effects of a legalization program. The discussion was moderated by Doris Meissner, MPI Senior Fellow and Director of the U.S. Immigration Policy Program, with comments from MPI Senior Policy Analyst Randy Capps and Sherrie A. Kossoudji, Associate Professor, School of Social Work, and Adjunct Professor, Department of Economics, University of Michigan.

Carbon emissions in 2014 remained at the previous year’s levels of 32.3 billion metric tons — a milestone that points to the impact worldwide renewable energy investment is having in the face of a 1.5 percent annual increase in global energy consumption, according to a new report from REN21. The tenth annual Renewables 2015 Global Status Report cites “increased penetration of renewable energy” and improvements in energy efficiency as the chief reasons for the noted emissions stabilization.

Acting US director of national intelligence Richard Grenell says he spoke "with an influential Lebanese Shi'ite leader" who is "close" to coming out publicly in favor of decriminalizing homosexuality

Professor Ashutosh Varshney of Brown University analyzes the current state of India's democratic system as well as the strengths and challenges in this rapidly growing nation. Full interview.

This interactive chart, designed by Krisztina Szucs and Mate Cziner from Hungary, condenses highly complex data on the costs and benefits of education around the world. It clearly highlights important facts showing students, parents and policy makers where the real costs and benefits lie for them in relation to education

Broadway star Ruthie Ann Miles, 37, has given birth to a baby girl and announced it on her Instagram. Hope Elizabeth was born last month to her and husband Jonathan Blumenstein.