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This edition of the "Virginia English Bulletin" is devoted primarily to articles about multiple-elective programs in high school English classes. These articles include: (1) "Multiple Electives in the English Curriculum" by R. Baird Shuman; (2) "Creative Dramatics: A Natural for the Multiple Electives Program" by Charles R. Duke; (3) "Spotsylvania Experiments with New Courses" by Donna Kolb; (4) "Canadian School Experiments with New Courses" by James Satterwaite; (5) "From Pole to Pole: The Teaching of World Literature as a Multiple Elective" by Robert T. Robertson; and (6) "English and Social Studies--The Academic Odd Couple" by Bernard S. Miller. A bibliography on high school phase-elective English programs prepared in August 1970 by NCTE/ERIC is also included. (Author/DI)

Although many factors lead students, particularly the culturally disadvantaged, to avoid reading, among the most significant reasons are an abhorrence of the kinds of readings contained in their English anthologies, and the physical characteristics of these books. If the schools are to encourage reading as a broadening experience, they must furnish students with interest-provoking materials which are easy to read at those places where their reading is normally done--on buses or at lunch counters, for example. One technique for improving the teaching of literature would be for the school to give each student, every year, 10 inexpensive paper back books of literary quality, yet of interest to them. These paperbacks are easily read in the student's natural reading situations, are comfortable to hold and transport, and could be marked by the student without fear of recrimination from the school. In addition, the student would begin to feel a pride in the ownership of books, and these books might become the first step in making reading a vital part of the life in culturally-disadvantaged homes. (DL)

Novel psychoactive substances (NPS) threaten public health and safety while also straining the limited resources of forensic laboratories. To efficiently allocate the finite resources available, we propose a new strategy for prioritizing NPS with abuse liability testing using a preclinical behavioral procedure in rats known as intracranial self-stimulation (ICSS). To validate this assay, the recently-scheduled synthetic cathinone α-PHP was compared to cocaine, a mechanistically similar drug of abuse, as a positive control and saline as a negative control. Male Sprague-Dawley rats (n=6) were implanted with electrodes targeting the medial forebrain bundle and trained to respond by lever-press for electrical brain stimulation. The rats were tested with doses of 0.32, 1.0, and 3.2 mg/kg α-PHP as well as 10 mg/kg of cocaine and saline administered by intraperitoneal injection. Neither saline nor 0.32 mg/kg α-PHP altered ICSS response rates compared to baseline levels of responding; however, doses of 1.0 and 3.2 mg/kg α-PHP and 10 mg/kg cocaine facilitated ICSS responding. This ICSS profile suggests that α-PHP has high abuse potential, with a rapid onset of effects and a long duration of action, and supports the decision to schedule this compound. This study demonstrates the ability of ICSS to distinguish between compounds of low and high potential for abuse. A strategy is proposed here to screen NPS using ICSS and classify emerging drugs into four priority categories for further analysis.

Background The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic has infected over 127 million people worldwide, with almost 2.8 million deaths at the time of writing. Since no lactating individuals were included in initial trials of vaccine safety and efficacy, research on SARS-CoV-2 vaccination in lactating women and the potential transmission of passive immunity to the infant through mother’s milk is needed to guide patients, clinicians, and policy makers on whether to recommend immunization during the worldwide effort to curb the spread of this virus. Research Aims (1) To determine whether SARS-CoV-2 specific immunoglobins are found in human milk after vaccination, and (2) to characterize the time course and types of immunoglobulins present. Methods A longitudinal cohort study of lactating women ( N = 7) who planned to receive both doses of the Pfizer-BioNTech or Moderna SARS-CoV-2 vaccine between December 2020 and January 2021 provided milk samples. These were collected pre-vaccination and at 11 additional timepoints, with the last sample at 14 days after the second dose of vaccine. Samples were analyzed for levels of SARS-CoV-2 specific immunoglobulins A and G (IgA and IgG). Results We observed significantly elevated levels of SARS-CoV-2 specific IgG and IgA antibodies in human milk beginning approximately 7 days after the initial vaccine dose, with an IgG-dominant response. Conclusions Maternal vaccination results in SARS-CoV-2 specific immunoglobulins in human milk that may be protective for infants.

Background Biliary atresia (BA), a newborn liver disease, is the leading cause of cirrhosis and liver-related death in children and the most common indication for pediatric liver transplantation (LT). The current standard of BA care is sequential surgery with an initial Kasai hepatoportoenterostomy (KP), followed by LT for those who progress to liver failure. Survival with native liver (SNL) correlates to infant age at KP with best outcome at early KP at Aims To assess age at BA presentation and subsequent investigations to the timing of KP and outcome. Methods A retrospective study of all BA cases referred to BC Children’s Hospital January 1, 2000-December 31, 2018. Data collection included age at referral, clinical presentation, laboratory and imaging studies, age at KP and LT. SNL and overall survival rates were determined. Descriptive statistics and data analyses using SSPS were applied. Results In this 19-year study, there were 48 cases (58% female) of BA in BC (1:17,000 live births). KP was performed in 41 patients and 7 had primary LT. Following the initial KP, 23 cases had LT. Median age at presentation decreased from 55 to 42 days after introduction of the BC BA stool card screening program in 2014. The Median (IQR) age at KP was 62 days (48–87). Median delay from the age at first encounter to the KP was 10 days (4–21); early referral (youngest 3rd of cohort) had a mean delay to KP of 25 days (15–40) compared with the late group (oldest 3rd of cohort) with median delay to KP of 5 days (1–8). There were 2.4 and 1.4 investigations/patient before undergoing KP in the youngest and oldest age at presentation cohorts. HIDA scan was done in 41% and 19% of the youngest and oldest presentation cohorts respectively. Median LT age was 9.6 months (8-13months). Median age at KP for patients who received LT was 77 days (53–92), compared to 52 days (41–79) in those without LT (p=0.08). All KPs were completed by 7 surgeons, each completing 1- 10 KPs. Overall patient survival and SNL were 98% and 37.5%. Conclusions In this cohort, SNL rates were below SNL rates in other national studies. SNL rates were higher in patients who underwent KP at a younger age, and early findings from a provincial screening program show a shift in age at presentation, potentially owing in part to increased community awareness of BA. A diagnostic algorithm that accounts for age at presentation is needed achieve timely KP. Funding Agencies None

We have investigated the addition of a simple phosphinoboronate ester, Ph2PBpin (pin = 1,2-O2C2Me4), to 2-diphenylphosphinobenzaldehyde (2-Ph2PC6H4C(O)H) and related aldimine derivatives (2-Ph2PC6H4C(NR)H) as a simple and effective strategy for generating unique diphosphine ligands bearing a pendant Lewis-acid Bpin group. These reactions proceed selectively to give one new product where the phosphide fragment has added to the aldehyde (or imine) carbon atom and the electron-deficient boron group has added to the electron-rich heteroatom. Preliminary studies show these new compounds can ligate to Pd(II) and Pt(II) metal centres. These novel metal complexes, as well as the organic soluble [MCl2(coe)]2 (M = Pd, Pt, coe = cis-cyclooctene) compounds, have been shown to be effective precatalysts in the cyclisation of alkynoic acids to give the corresponding exo-dig cyclic lactones. Reactions employing these metal complexes also generated unusual endo-dig cyclic lactones not traditionally observed in these cyclisation reactions. For instance, reactions of 4-pentynoic acid also afforded significant amounts of α-angelica lactone, a biologically-important compound traditionally prepared via the catalytic dehydration and cyclisation of levulinic acid.

ImportanceThe SARS-CoV-2 pandemic has infected over a hundred million people worldwide, with almost 2.5 million deaths at the date of this publication. In the United States, Pfizer-BioNTech and Moderna vaccines were first administered to the public starting in December 2020, and no lactating women were included in the initial trials of safety/efficacy. Research on SARS-CoV-2 vaccination in lactating women and the potential transmission of passive immunity to the infant through breast milk is needed to guide patients, clinicians and policy makers during the worldwide effort to curb the spread of this virus.ObjectiveTo determine whether SARS-CoV-2 specific immunoglobins are found in breast milk post-vaccination, and to characterize the time course and types of immunoglobulins present.DesignProspective cohort studySettingProvidence Portland Medical Center, Oregon, USAParticipantsSix lactating women who planned to receive both doses of the Pfizer-BioNTech or Moderna vaccine between December 2020 and January 2021. Breast milk samples were collected pre-vaccination and at 11 additional timepoints, with last sample at 14 days post 2nd dose of vaccine.ExposureTwo doses of Pfizer-BioNTech or Moderna SARS-CoV-2 vaccine.Main Outcome(s) and Measure(s)Levels of SARS-CoV-2 specific IgA and IgG immunoglobulins in breast milk.ResultsIn this cohort of 6 lactating women who received 2 doses of SARS-CoV-2 vaccine, we observed significantly elevated levels of SARS-CoV-2 specific IgG and IgA antibodies in breast milk beginning at Day 7 after the initial vaccine dose, with an IgG-dominant response.Conclusions and RelevanceWe are the first to show that maternal vaccination results in SARS-CoV-2 specific immunoglobulins in breast milk that may be protective for infants.

Background The phase III CLinical Evaluation Of Pertuzumab And TRAstuzumab (CLEOPATRA) trial established the combination of pertuzumab, trastuzumab and docetaxel as standard first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive locally recurrent/metastatic breast cancer (LR/mBC). The multicentre single-arm PERtUzumab global SafEty (PERUSE) study assessed the safety and efficacy of pertuzumab and trastuzumab combined with investigator-selected taxane in this setting. Patients and methods Eligible patients with inoperable HER2-positive LR/mBC and no prior systemic therapy for LR/mBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab and pertuzumab until disease progression or unacceptable toxicity. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Prespecified subgroup analyses included subgroups according to taxane, hormone receptor (HR) status and prior trastuzumab. Exploratory univariable analyses identified potential prognostic factors; those that remained significant in multivariable analysis were used to analyse PFS and OS in subgroups with all, some or none of these factors. Results Of 1436 treated patients, 588 (41%) initially received paclitaxel and 918 (64%) had HR-positive disease. The most common grade ≥3 adverse events were neutropenia (10%, mainly with docetaxel) and diarrhoea (8%). At the final analysis (median follow-up: 5.7 years), median PFS was 20.7 [95% confidence interval (CI) 18.9-23.1] months overall and was similar irrespective of HR status or taxane. Median OS was 65.3 (95% CI 60.9-70.9) months overall. OS was similar regardless of taxane backbone but was more favourable in patients with HR-positive than HR-negative LR/mBC. In exploratory analyses, trastuzumab-pretreated patients with visceral disease had the shortest median PFS (13.1 months) and OS (46.3 months). Conclusions Mature results from PERUSE show a safety and efficacy profile consistent with results from CLEOPATRA and median OS exceeding 5 years. Results suggest that paclitaxel is a valid alternative to docetaxel as backbone chemotherapy. Exploratory analyses suggest risk factors that could guide future trial design.

The innate immune response to cytosolic DNA involves transcriptional activation of type I interferons (IFN-I) and proinflammatory cytokines. This represents the culmination of intracellular signaling pathways that are initiated by pattern recognition receptors that engage DNA and require the adaptor protein Stimulator of Interferon Genes (STING). These responses lead to the generation of cellular and tissue states that impair microbial replication and facilitate the establishment of long-lived, antigen-specific adaptive immunity. Ultimately this can lead to immune-mediated protection from infection but also to the cytotoxic T cell-mediated clearance of tumor cells. Intriguingly, pharmacologic activation of STING-dependent phenotypes is known to enhance both vaccine-associated immunogenicity and immune-based anti-tumor therapies. Unfortunately, the STING protein exists as multiple variant forms in the human population that exhibit differences in their reactivity to chemical stimuli and in the intensity of molecular signaling they induce. In light of this, STING-targeting drug discovery efforts require an accounting of protein variant-specific activity. Herein we describe a small molecule termed M04 that behaves as a novel agonist of human STING. Importantly, we find that the molecule exhibits a differential ability to activate STING based on the allelic variant examined. Furthermore, while M04 is inactive in mice, expression of human STING in mouse cells rescues reactivity to the compound. Using primary human cells in ex vivo assays we were also able to show that M04 is capable of simulating innate responses important for adaptive immune activation such as cytokine secretion, dendritic cell maturation, and T cell cross-priming. Collectively, this work demonstrates the conceivable utility of a novel agonist of human STING both as a research tool for exploring STING biology and as an immune potentiating molecule.

Methcathinone (MCAT; 1), the progenitor of numerous and widely abused “synthetic cathinone” central stimulants, exists as a pair of optical isomers. Although S(−)MCAT is several-fold more potent than R(+)MCAT in rodent locomotor stimulation and in stimulus generalization studies in rat drug discrimination assays, the individual optical isomers of MCAT have never been directly compared for their actions at monoamine transporters that seem to underlie their actions, and have never been examined for their relative abuse potential. Here, we found that the isomers of MCAT are nearly equi-effective at dopamine and norepinephrine transporters (DAT and NET, respectively) as transporter substrates (i.e., as releasing agents), and are ≥63-fold less potent at the serotonin transporter (SERT). In intracranial self-stimulation (ICSS) studies to evaluate abuse-related drug effects in rats, S(−)MCAT was approximately twice as potent as its R-enantiomer. Achiral analogs, α-methyl MCAT (3) and α-des-methyl MCAT (4), also were DAT/NET substrates and also produced abuse-related ICSS effects, indicating that they retain abuse potential and that they might be useful for the further study of the stereochemistry of synthetic cathinone analogs with chiral β- (or other) substituents.

Conversion of the ocean’s vertical thermal energy gradient to electricity via Ocean Thermal Energy Conversion (OTEC) has been demonstrated at small scales over the past century, and represents one of the largest (and growing) potential energy sources on the planet. Here we describe how OTEC could be modified to provide a large source of CO2-emissions-negative energy while also allowing heat removal from the surface ocean, helping to directly counter ocean/atmosphere warming. Most OTEC energy potential is far offshore, thus the conversion of the produced electricity to a chemical energy carrier such as H2 or derivatives is required. This can be achieved by employing a method of electrochemically generating H2 that also consumes CO2, converting the carbon to a common form of ocean alkalinity. The addition of such alkalinity to the ocean would provide high-capacity carbon storage while countering the chemical and biological effects of ocean acidification. For each gigawatt (GW) of continuous electric power generated over one year by the preceding negative-emissions OTEC (NEOTEC), roughly 13 GW of surface ocean heat would be directly removed to deep water, while producing 1.3 × 105 tonnes of H2/yr (avoiding 1.1 × 106 tonnes of CO2 emissions/yr), and consuming and storing (as dissolved mineral bicarbonate) approximately 5 × 106 tonnes CO2/yr. The preceding CO2 mitigation would result in an indirect planetary cooling effect of about 2.6 GW. Such negative-emissions energy production and global warming mitigation would avoid the biophysical and land use limitations posed by methods that rely on terrestrial biology.

Electronic cigarettes (e-cigs) deliver nicotine in an aerosol to the user that simulates the smoke of traditional cigarettes purportedly without the pathology of inhaling tobacco smoke due to the absence of combustion. Advanced versions of e-cigs enable the user to potentially moderate the concentration of drug in the aerosol by selecting from a range of voltages on the power supply. A method was developed to trap the aerosol produced by a KangerTech AeroTank, 1.8 Ω preassembled atomizer in order to analyze the concentration of nicotine and to evaluate the constituents of the aerosol at various voltages on the power supply. A 12-mg/mL formulation of nicotine in 50:50 propylene glycol (PG):vegetable glycerin (VG) was used to produce aerosol at 3.9, 4.3 and 4.7 V. The aerosol was trapped in a simple glass assemblage and analyzed by a 3200 Q Trap HPLC-MS-MS. The dose of nicotine delivered in the aerosol at 3.9, 4.3 and 4.7 V was determined to be 88 ± 12 μg, 91 ± 15 μg and 125 ± 22 μg. The average recovery of nicotine in the trap across the voltages was 99.8%. The glass trap system was an effective device for collecting the aerosol for analysis and an increase in drug yield was observed with increasing voltage from the power supply on the e-cig. The glass trap system was also used in combination with a 100-μm solid-phase microextraction fiber to capture the aerosol and analyze it via DART-MS and GC-MS. Four commercial e-liquids labeled to contain nicotine were aerosolized at 4.3 V. The pharmacologically active ingredient, nicotine, as well as PG, VG and a number of flavoring agents found in these formulations were identified.

Purpose The role of MerTK, a member of the Tyro3-Axl-MerTK family of receptor tyrosine kinase, in the immune response to radiation therapy (RT) is unclear. We investigated immune-mediated tumor control after RT in murine models of colorectal and pancreatic adenocarcinoma using MerTK wild-type and knock-out hosts and whether inhibition of MerTK signaling with warfarin could replicate MerTK knock-out phenotypes. Methods and Materials Wild-type and MerTK–/– BALB/c mice were grafted in the flanks with CT26 tumors and treated with computed tomography guided RT. The role of macrophages and CD8 T cells in the response to radiation were demonstrated with cell depletion studies. The role of MerTK in priming immune responses after RT alone and with agonist antibodies to the T cell costimulatory molecule OX40 was evaluated in a Panc02-SIY model antigen system. The effect of warfarin therapy on the in-field and abscopal response to RT was demonstrated in murine models of colorectal adenocarcinoma. The association between warfarin and progression-free survival for patients treated with SABR for early-stage non-small cell lung cancer was evaluated in a multi-institutional retrospective study. Results MerTK–/– hosts had better tumor control after RT compared with wild-type mice in a macrophage and CD8 T cell–dependent manner. MerTK–/– mice showed increased counts of tumor antigen-specific CD8 T cells in the peripheral blood after tumor-directed RT alone and in combination with agonist anti-OX40. Warfarin therapy phenocopied MerTK–/– for single-flank tumors treated with RT and improved abscopal responses for RT combined with anti-CTLA4. Patients on warfarin therapy when treated with SABR for non-small cell lung cancer had higher progression-free survival rates compared with non–warfarin users. Conclusions MerTK inhibits adaptive immune responses after SABR. Because warfarin inhibits MerTK signaling and phenocopies genetic deletion of MerTK in mice, warfarin therapy may have beneficial effects in combination with SABR and immune therapy in patients with cancer.

Syntheses are reported for: nine 2-nitroimidazoles, the abbreviated names all beginning with E, based on derivation from Etanidazole); five 2-methyl-5-nitroimidazoles (M compounds, derived from Metronidazole); and five 2-methyl-4-nitroimidazoles (labelled 2M4N compounds). The nitroimidazoles all have an amide side-chain at the N1 atom of the imidazole, with 17 of them containing one to five halogen atoms. The aim is to study compounds for comparison with EF5 (the number showing the presence of five F-atoms), a previously reported, pentafluoropropylacetamide derivative of 2-nitroimidazole that is currently used as a hypoxia marker drug to detect cancerous tumours. The new compounds are characterized by standard methods, including X-ray structural data for the fluorinated MF5, 2M4NF5, and 2M4NF1(−1) species, with the “–1” indicating two C-atoms in an alkylamide chain rather than the three C-atoms in the propylacetamide of EF5. Intra- and inter-molecular H-bonding is seen in the solid state structures, likely an important property in biological use; another key property of the nitroimidazoles is their reduction potentials, and the measured CV data confirm that 2NO2Im compounds with longer side-chains and more F-atoms (like EF5) are worth investigating for possible activity as hypoxia-selective, bioreductive agents.

Although prophylactic vaccines provide protective humoral immunity against infectious agents, vaccines that elicit potent CD8 T cell responses are valuable tools to shape and drive cellular immunity against cancer and intracellular infection. In particular, IFN-γ–polarized cytotoxic CD8 T cell immunity is considered optimal for protective immunity against intracellular Ags. Suppressor of cytokine signaling (SOCS)1 is a cross-functional negative regulator of TLR and cytokine receptor signaling via degradation of the receptor–signaling complex. We hypothesized that loss of SOCS1 in dendritic cells (DCs) would improve T cell responses by accentuating IFN-γ–directed immune responses. We tested this hypothesis using a recombinant Listeria monocytogenes vaccine platform that targets CD11c+ DCs in mice in which SOCS1 is selectively deleted in all CD11c+ cells. Unexpectedly, in mice lacking SOCS1 expression in CD11c+ cells, we observed a decrease in CD8+ T cell response to the L. monocytogenes vaccine. NK cell responses were also decreased in mice lacking SOCS1 expression in CD11c+ cells but did not explain the defect in CD8+ T cell immunity. We found that DCs lacking SOCS1 expression were functional in driving Ag-specific CD8+ T cell expansion in vitro but that this process was defective following infection in vivo. Instead, monocyte-derived innate TNF-α and inducible NO synthase–producing DCs dominated the antibacterial response. Thus, loss of SOCS1 in CD11c+ cells skewed the balance of immune response to infection by increasing innate responses while decreasing Ag-specific adaptive responses to infectious Ags.

Most previous brief intervention (BI) studies have focused on alcohol or drug use, instead of both substances. Our primary aim was to determine if an alcohol- and drug-use BI reduced alcohol use and increased alcohol treatment services utilization among adult emergency department (ED) patients who drink alcohol and require an intervention for their drug use. Our secondary aims were to assess when the greatest relative reductions in alcohol use occurred, and which patients (stratified by need for an alcohol use intervention) reduced their alcohol use the most. In this secondary analysis, we studied a sub-sample of participants from the Brief Intervention for Drug Misuse in the Emergency Department (BIDMED) randomized, controlled trial of a BI vs. no BI, whose responses to the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) indicated a need for a BI for any drug use, and who also reported alcohol use. Participants were stratified by their ASSIST alcohol subscore: 1) no BI needed, 2) a BI needed, or 3) an intensive intervention needed for alcohol use. Alcohol use and alcohol treatment services utilization were measured every 3 months for 12 months post-enrollment. Of these 833 participants, median age was 29 years-old, 46% were female; 55% were white/non-Hispanic, 27% black/non-Hispanic, and 15% Hispanic. Although any alcohol use, alcohol use frequency, days of alcohol use, typical drinks consumed/day, and most drinks consumed/day decreased in both the BI and no BI arms, there were no differences between study arms. Few patients sought alcohol use treatment services in follow-up, and utilization also did not differ by study arm. Compared to baseline, alcohol use reduced the most during the first 3 months after enrollment, yet reduced little afterward. Participants whose ASSIST alcohol subscores indicated a need for an intensive intervention generally had the greatest relative decreases in alcohol use. These results indicate that the BI was not efficacious in reducing alcohol use among alcohol- and drug-using adult ED patients than the self-assessments alone, but suggest that self-assessments with or without a BI may confer reductions in alcohol use.

The ability to perceive such things as nuances of language, moods of people, and the temper of society may be the single most important ability students need to develop. One approach, which works well with upper elementary and junior high students, uses units involving community study with library research, observation, and interviewing as a base. Committees of students are organized to observe and examine aspects of community life--e.g., occupational opportunities, educational and transportation facilities, and language and cultural differences. This examination of community life leads into a study of literature, particularly the short story, which further develops the students' skills of observation and perception. (JM)

The number of drivers using drugs has increased over the last few years, and is likely to continue its upward trend. Testing drivers for alcohol use is routine and standardized, but the same is not true for the identification of driving under the influence of drugs (DUID). The Drug Evaluation and Classification Program (DECP) was developed to train police officers to recognize the signs and symptoms of recent drug use and remains an invaluable program; however, there are insufficient numbers of these highly trained drug recognition experts (DREs) available to attend every potential drug involved traffic incident. While blood and urine samples are used to test for drugs in a driver, both have disadvantages, particularly as they pertain to the length of time required after a traffic stop to sample collection. Therefore, the development of oral fluid testing devices which can be operated at the roadside and have the potential to assist officers in the identification of drug use is a major advancement in DUID cases. This project evaluated the performance of one instrumental oral fluid roadside testing device (Alere DDS®2) compared to DRE opinion, oral fluid laboratory-based analysis, and routine blood testing. The results showed that there was a good correlation with DRE observations and the device performance was >80% in all drug categories compared to laboratory-based analytical testing, both in oral fluid and blood, with few exceptions. The instrument can be considered a useful tool to assist law enforcement in identifying a drugged driver. Because the device does not test for all potentially impairing drugs, the opinion of the police officer regarding the condition of the driver should still be considered the most important aspect for arrest and further action.

The Ru III complexes, [Ru(acac) 2 L 2 ] Tf, and the Ru II complexes, Ru(hfac) 2 L 2 , have been synthesized and characterized; acac = acetylacetonate, hfac = 1,1,1,5,5,5-hexafluoroacetonate, Tf = triflate, and L = imidazole (Im) or a substituted imidazole (NMeIm, 2MeIm, 4/5MeIm, 2NO 2 Im); other nitroimidazoles, named metronidazole, etanidazole, and EF5 (a pentafluorinated derivative of etanidazole) were also used. Cis -isomers of the Ru complexes were usually formed, but some trans -isomers were also isolated. Characterization methods include NMR, UV/Vis, and MS spectroscopies, and CV data; X-ray crystallographic data were obtained for the cis -[Ru(acac) 2 L 2 ]Tf complexes (L = Im, NMeIm, 2MeIm, and 5MeIm). Interest in these complexes stems from their potential antiproliferatory activity, and use of the nitroimidazole species as radiosensitizers. More incidentally synthesized were cis -[Ru(acac) 2 L(MeCN)]Tf (L = Im, 2MeIm), cis -Ru(hfac) 2 Im(MeCN), and [Ru(hfac)(NMeIm) 4 ]PF 6 .

Nucleic acid sensing pathways have likely evolved as part of a broad pathogen sensing strategy intended to discriminate infectious agents and initiate appropriate innate and adaptive controls. However, in the absence of infectious agents, nucleic acid sensing pathways have been shown to play positive and negative roles in regulating tumorigenesis, tumor progression and metastatic spread. Understanding the normal biology behind these pathways and how they are regulated in malignant cells and in the tumor immune environment can help us devise strategies to exploit nucleic acid sensing to manipulate anti-cancer immunity.