S100A8/A9 predicts response to PIM kinase and PD-1/PD-L1 inhibition in triple-negative breast cancer mouse models.

Background: Understanding why some triple-negative breast cancer (TNBC) patients respond poorly to existing therapies while others respond well remains a challenge. This study aims to understand the potential underlying mechanisms distinguishing early-stage TNBC tumors that respond to clinical intervention from non-responders, as well as to identify clinically viable therapeutic strategies, specifically for TNBC patients who may not benefit from existing therapies.

Methods: We conducted retrospective bioinformatics analysis of historical gene expression datasets to identify a group of genes whose expression levels in early-stage tumors predict poor clinical outcomes in TNBC.

S100A8/A9 predicts triple-negative breast cancer response to PIM kinase and PD-1/PD-L1 inhibition.

It remains elusive why some triple-negative breast cancer (TNBC) patients respond poorly to existing therapies while others respond well. Our retrospective analysis of historical gene expression datasets reveals that increased expression of immunosuppressive cytokine S100A8/A9 in early-stage tumors is robustly associated with subsequent disease progression in TNBC. Although it has recently gained recognition as a potential anticancer target, S100A8/A9 has not been integrated into clinical study designs evaluating molecularly targeted therapies.

Think globally, act locally: Quality improvement as a catalyst for COVID-19 related care during the transitional years.

The COVID-19 pandemic has posed distinctive challenges to adolescents and young adults living with spina bifida, especially those from ethic minority populations. With this public health challenge in mind, developing a customized electronic health record to leverage registry data to promote and quantify COVID-19 vaccination uptake among this population is feasible. We provide a brief description of our activities in customizing an electronic health record to track vaccination uptake among adolescents and young adults with spina bifida (AYASB); and the lessons learned, in hopeful support of those scaling-up vaccination delivery across the globe for AYASB as they transition to adult-centered care.

Synergistic PIM kinase and proteasome inhibition as a therapeutic strategy for MYC-overexpressing triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is the breast cancer subtype with the poorest clinical outcome. The PIM family of kinases has emerged as a factor that is both overexpressed in TNBC and associated with poor outcomes. Preclinical data suggest that TNBC with an elevated MYC expression is sensitive to PIM inhibition.

Pulsed-field gel electrophoresis for long-range restriction mapping.

This unit describes procedures for generating long-range restriction maps of genomic DNA and for analysis of large insert clones. The basic protocol details restriction digestion of agarose-embedded DNA, PFGE separation, Southern transfer, and hybridization. Support protocols describe the preparation of high-molecular-weight genomic DNA samples in agarose blocks and in agarose microbeads, respectively.

Purification and characterization of YACs containing large inserts.

This unit provides protocols for characterizing DNA segments cloned in YACs and for purifying YACs from yeast chromosomes. The first basic protocol describes Southern blotting and partial-digest restriction analysis of YACs. These methods are useful for determining the size and complexity of the cloned insert DNA, the presence and location of particular restriction sites or sequences, and even the species of origin of the insert DNA (indicated by hybridization to species-specific repetitive elements such as Alu repeats).

Pharmacokinetics and safety of an anti-vascular endothelial growth factor aptamer (NX1838) following injection into the vitreous humor of rhesus monkeys.

Purpose: The objective of this study was to determine the pharmacokinetics and safety for NX1838 following injection into the vitreous humor of rhesus monkeys.

Methods: Plasma and vitreous humor pharmacokinetics were determined following a single bilateral 0.25, 0.

Monoclonal antibody mapping of the envelope glycoprotein of the dengue 2 virus, Jamaica.

Although dengue (DEN) virus is the etiologic agent of dengue fever, the most prevalent vector-borne viral disease in the world, precise information on the antigenic structure of the dengue virion is limited. We have prepared a set of murine monoclonal antibodies (MAbs) specific for the envelope (E) glycoprotein of DEN 2 virus and used these antibodies in a comprehensive biological and biochemical analysis to identify 16 epitopes. Following domain nomenclature developed for the related flavivirus, tick-borne encephalitis, three functional domains were identified.

The Northridge earthquake: community-based approaches to unmet recovery needs.

The 1994 Northridge, California earthquake has proven to be one of the most costly disasters in United States history. Federal and state assistance programmes received some 681,000 applications from victims for various forms of relief. In spite of the flow of US$11 billion in federal assistance into Los Angeles and Ventura counties, many victims have failed to obtain adequate relief.

Monoclonal antibodies capable of distinguishing epizootic from enzootic varieties of subtype 1 Venezuelan equine encephalitis viruses in a rapid indirect immunofluorescence assay.

We used previously characterized murine monoclonal antibodies to develop a panel useful in subtyping Venezuelan equine encephalitis (VEE) viruses by an indirect fluorescent antibody assay. This panel worked well with either prototype VEE viruses or a series of more recent VEE virus isolates. The panel is particularly useful for rapidly differentiating VEE viruses with epidemic-epizootic potential from other endemic varieties of this virus.

Steam Vacuuming as a Pre-Evisceration Intervention To Decontaminate Beef Carcasses.

One steam-vacuuming unit (Unit A) was evaluated for removal of visible contamination and reduction of bacterial counts on beef carcass surfaces in five processing plants; a second steam-vacuuming unit (Unit B) was evaluated in two of those same plants at a later date. Experimental treatments included appropriate Controls: steam vacuuming carcass surfaces with or without visible contamination, and knife trimming surfaces with visible contamination. Depending on the processing plant, carcasses were tested on the midline or on the round.

YAC contigs covering an 8-megabase region of 3p deleted in the small-cell lung cancer cell line U2020.

Somatic deletions of chromosome 3p occur at high frequencies in cancers of kidney, breast, cervix, head and neck, nasopharynx, and lung. The frequency of 3p deletion in lung cancer approaches 100% among small cell lesions and 70 to 80% in non-small cell lesions. This evidence strongly implies that one or more tumor suppressor genes of potentially widespread significance reside within the deleted region(s).

The Murray Valley encephalitis virus prM protein confers acid resistance to virus particles and alters the expression of epitopes within the R2 domain of E glycoprotein.

To study the role of the precursor to the membrane protein (prM) in flavivirus maturation, we inhibited the proteolytic processing of the Murray Valley encephalitis (MVE) virus prM to membrane protein in infected cells by adding the acidotropic agent ammonium chloride late in the virus replication cycle. Viruses purified from supernatants of ammonium chloride-treated cells contained prM protein and were unable to fuse C6/36 mosquito cells from without. When ammonium chloride was removed from the cells, both the processing of prM and the fusion activity of the purified viruses were partially restored.

Beta-alanine transaminase activity in black and suppressor of black mutations of Drosophila melanogaster.

An assay for beta-alanine transaminase activity in extracts of Drosophila melanogaster has been developed. By use of this assay, the levels of beta-alanine transaminase activity in several strains of flies has been examined as a function of developmental age. The black mutation shows elevated levels of activity compared to wild type, while suppressor of black strains show decreased levels compared to wild type.

Synthetic peptides of the E2 glycoprotein of Venezuelan equine encephalomyelitis virus. II. Antibody to the amino terminus protects animals by limiting viral replication.

A peptide composed of the amino-terminal 25 amino acids of the E2 glycoprotein of the virulent Trinidad donkey (TRD) strain of Venezuelan equine encephalomyelitis virus was found to protect peptide-immunized mice from lethal TRD virus challenge (Hunt et al., 1990). Viral growth in peptide-immunized animals was found to be limited in comparison to that in nonimmunized controls.

Shelter, housing and recovery: a comparison of u.s. Disasters.

In this paper we examine the issues associated with the temporary sheltering and housing of victims after natural disasters in the United States. Specific topics addressed include differential access to shelter and housing aid according to social class, ethnicity and related demographic factors; the relationship between post-disaster shelter and housing and long-term recovery; the role of social support networks in the sheltering of victims; and the implications of the research for the provision of shelter and housing aid after disasters.

Use of a new synthetic-peptide-derived monoclonal antibody to differentiate between vaccine and wild-type Venezuelan equine encephalomyelitis viruses.

We have prepared a murine monoclonal antibody (MAb) capable of distinguishing between wild-type Venezuelan equine encephalomyelitis (VEE) virus and the TC-83 vaccine derivative. This MAb, 1A2B-10, was derived from immunization with a synthetic peptide corresponding to the first 19 amino acids of the E2 glycoprotein of Trinidad donkey VEE virus. The MAb reacts with prototype viruses from all naturally occurring VEE subtypes except subtype 6 in an enzyme-linked immunosorbent assay.

Antibodies to dengue 2 virus E-glycoprotein synthetic peptides identify antigenic conformation.

Eighteen synthetic peptides have now been prepared from dengue (DEN) 2 virus, representing 80% of the extra-membranal domain of the DEN envelope (E)-glycoprotein. These peptides were selected based upon our previous results with Murray Valley encephalitis (MVE) virus, computer analysis of the DEN virus sequence, and the predicted E-glycoprotein secondary structure. Six of these peptides were "structural" peptides derived from either nonlinear amino acid sequences or predicted disulfide bridge-stabilized loop structures.

Identification of monoclonal antibodies capable of differentiating antigenic varieties of eastern equine encephalitis viruses.

We have isolated and characterized 3 monoclonal antibody (Mab) reagents useful in the serological identification of varieties of eastern equine encephalitis (EEE) viruses. These antibodies were specific for the E1 glycoprotein of their homologous viruses. One Mab, 1B5C-3, reacted specifically with all North American (NA) EEE viruses isolated over a 50 year period.

Surveillance of St. Louis encephalitis virus vectors in Grand Junction, Colorado, in 1987.

Grand Junction, Colorado, was the site of a St. Louis encephalitis (SLE) outbreak in 1985. Epidemiologic and ecologic investigations in 1985 and 1986 suggested that Culex tarsalis may not have been the exclusive vector in the outbreak and that Cx.

Effect of leukotrienes B4, C4, and D4 on segmental pulmonary vascular pressures.

Leukotrienes (LTs) C4 and D4 are vasoconstrictors and are thought to increase both systemic and pulmonary vascular permeability. However, we and others have observed that LTC4 and LTD4 cause pulmonary vasoconstriction but do not increase the fluid filtration coefficient of excised guinea pig lungs perfused with a cell-depleted perfusate. To determine what vascular segments were exposed to an LT-induced increase in intravascular hydrostatic pressure we measured pulmonary arterial (Ppa), pulmonary arterial occlusion (Po,a), venous (Po,v) and double occlusion (Pdo) pressures in isolated guinea pig lungs perfused with a cell-depleted buffered salt solution before and after injecting 4 micrograms of LTB4, LTC4, or LTD4 into the pulmonary artery.

Stability of St. Louis encephalitis viral antigen detected by enzyme immunoassay in infected mosquitoes.

The use of enzyme immunoassay to detect St. Louis encephalitis (SLE) viral antigen in vector mosquitoes enhances the effectiveness of surveillance because infected mosquitoes can be identified more rapidly than with conventional virus isolation systems and because it is a simple and accessible procedure. Infectivity among mosquitoes experimentally infected with SLE virus was lost within 24 h after the mosquitoes were stored at 27 degrees C and 80% relative humidity; however, viral antigen remained stable under these conditions and could be detected by enzyme immunoassay 2 weeks later.

Glycolysis is not required for fluid homeostasis in isolated rabbit lungs.

We investigated whether glycolysis was necessary to maintain the integrity of vascular endothelial and alveolar epithelial barriers in continually weighed isolated rabbit lungs. Lungs were perfused with a cell-free buffered salt solution, and glycolysis was inhibited with a glucose analogue (alpha-methyl glucoside, alpha-MG) or one of two glycolysis inhibitors (iodoacetic acid, IAA, or NaF). Fluid filtration rates (FFR's, the change in lung weight/time) in response to a 7.

Older people in disaster: a comparison of black and white victims.

This research examines differential vulnerability to environmental stressors among white and black elderly and non-elderly disaster victims. The research identifies the determinants of psychosocial recovery for those four demographic groups. A total of 431 families who were victims of a tornado were interviewed for the study.