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PurposeThe team voice (TV) concept has been largely understudied, with different definitions and understandings among prior research creating confusion for readers and future researchers. This study proposes a unified definition and connotation of TV that captures TV's collective meaning and highlights TV's vital role in Eastern contexts.Design/methodology/approachThis study applied the constructivist grounded theory (CGT) methodology to collect and analyze qualitative data from Vietnam software companies. A total of 32 software development managers and employees were interviewed regarding TV behavior of the managers and employees.FindingsThe findings emphasize that TV should not be understood as team members' average or aggregate voice. Rather, TV should be understood as the shared voice of team members toward higher management, other teams or individuals in the organization in an attempt to challenge/change the status quo [team collective voice (TCV)]. The findings also reveal the characteristics of TCV (purpose, voicing and consensus mechanisms), TCV's different types and important roles in the context of an Eastern country operating under weak institutions.Originality/valueThis exploratory study was able to clarify different connotations of employee voice at the team level, which helps raise awareness among scholars on the collective nature of TV and guides successive researchers away from inconsistent understandings of the term. The study also reveals certain institutional conditions that foster this type of voice and suggests the employee voice concept should not be examined independently from the concept's institutional context. The proposed typology contributes comprehensively to this conceptual work of TCV as the topology reveals the concept's multidimensionality and aids future research on measurement construction.

Resolving the spatial distribution of RNA and protein in tissues at subcellular resolution is a challenge in the field of spatial biology. We describe spatial molecular imaging, a system that measures RNAs and proteins in intact biological samples at subcellular resolution by performing multiple cycles of nucleic acid hybridization of fluorescent molecular barcodes. We demonstrate that spatial molecular imaging has high sensitivity (one or two copies per cell) and very low error rate (0.0092 false calls per cell) and background (~0.04 counts per cell). The imaging system generates three-dimensional, super-resolution localization of analytes at ~2 million cells per sample. Cell segmentation is morphology based using antibodies, compatible with formalin-fixed, paraffin-embedded samples. We measured multiomic data (980 RNAs and 108 proteins) at subcellular resolution in formalin-fixed, paraffin-embedded tissues (nonsmall cell lung and breast cancer) and identified18 distinct cell types, ten unique tumor microenvironments and 100 pairwise ligand-receptor interactions. Data on800,000 single cells and ~260 million transcripts can be accessed at http://nanostring.com/CosMx-dataset .

Municipal Solid Waste (MSW) refers to solid waste generated by towns and cities from different types of household activities1. Over 2 billion tons of MSW are produced annually. Improper disposal can lead to adverse health outcomes through water, soil and air contamination. Hazardous waste or unsafe waste treatment such as open burning can directly harm waste workers or other people involved in waste burning and neighbouring communities. At the same time, in order to keep up with the need in development, the energy demand also increasing. Therefore, utilize MSW to produce energy is gaining more recognition from public interest. Gasification offers some advantages over traditional method of utilize MSW (incineration, compost). Gasification plants produce significantly lower quantities of air pollutants. The process reduces the environmental impact of waste disposal because it allows for the use of waste products as a feedstock. In this paper, Aspen Plus software was deployed to assess and predict the outcome of the gasification process of MSW. The model was calibrated and validated with various observed data. The condition of input MSW and biomass, as well as the gasification agent were considered. The results revealed that primary products of gasification process are similar to other previously conducted experiments.

Defensive symbionts protect their hosts against imminent threats. A new study uncovers a symbiosis whereby a fungus safeguards its beetle host from predation, but also exploits the beetle as a vector to help it attack plants and cause disease.

Summary of exome sequence analysis of ten Taiwanese ccRCC patients

Description of Taiwanese ccRCC cohort

Circus plots of Taiwanese ccRCCs.

Primers used for Sanger sequencing

Background:Aristolochia species used in the practice of traditional herbal medicine contains aristolochic acid (AA), an established human carcinogen contributing to urothelial carcinomas of the upper urinary tract. AA binds covalently to genomic DNA, forming aristolactam (AL)–DNA adducts. Here we investigated whether AA is also an etiologic factor in clear cell renal cell carcinoma (ccRCC).Methods: We conducted a population-based case–control study to investigate the linkage between Aristolochia prescription history, cumulative AA consumption, and ccRCC incidence in Taiwan (5,709 cases and 22,836 matched controls). The presence and level of mutagenic dA-AL-I adducts were determined in the kidney DNA of 51 Taiwanese ccRCC patients. The whole-exome sequences of ccRCC tumors from 10 Taiwanese ccRCC patients with prior exposure to AA were determined.Results: Cumulative ingestion of more than 250 mg of AA increased risk of ccRCC (OR, 1.25), and we detected dA-AL-I adducts in 76% of Taiwanese ccRCC patients. Furthermore, the distinctive AA mutational signature was evident in six of 10 sequenced ccRCC exomes from Taiwanese patients.Conclusions: This study strongly suggests that AA contributes to the etiology of certain RCCs.Impact: The current study offers compelling evidence implicating AA in a significant fraction of the RCC arising in Taiwan and illustrates the power of integrating epidemiologic, molecular, and genetic data in the investigation of cancer etiology. Cancer Epidemiol Biomarkers Prev; 25(12); 1600–8. ©2016 AACR.

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Somatic mutations identified from exome sequencing of ten Taiwanese ccRCC patients

Surface patterning of inorganic nanoparticles through site-selective functionalization with mixed-ligand shells or additional inorganic material is an intriguing approach to developing tailored nanomaterials with potentially novel and/or multifunctional properties. The unique physicochemical properties of such nanoparticles are likely to impact their behavior and functionality in biological environments, catalytic systems, and electronics applications, making it vital to understand how we can achieve and characterize such regioselective surface functionalization. This Feature Article will review methods by which chemists have selectively modified the surface of colloidal nanoparticles to obtain both two-sided Janus particles and nanoparticles with patchy or stripey mixed-ligand shells, as well as to achieve directed growth of mesoporous oxide materials and metals onto existing nanoparticle templates in a spatially and compositionally controlled manner. The advantages and drawbacks of various techniques used to characterize the regiospecificity of anisotropic surface coatings are discussed, as well as areas for improvement, and future directions for this field.

The results of mechanical thrombectomy (MT), wi-thout or with intravenous thrombolysis, were evaluated and compared in 178 patients with acute ischemic stroke (AIS) due to large vessel occlusions (LVO) at Bach Mai Hospital.A total of 178 patients with AIS due to LVO were assigned to undergo MT alone (MT-alone group) or MT preceded by intravenous alteplase (the combined group), at a dose of 0.9 mg per kilogram, administered within 4.5 hours after symptom onset (combined group). The successful recanalization rate (assessed as thrombolysis in cerebral infarction [TICI] classification of 2b-3) and the incidence of good clinical recovery outcomes (modified Rankin Scale [mRS] ≤2) after 3 months were analyzed in both groups and compared.A total of 178 patients were enrolled (median age, 65 years; 55% men; median National Institutes of Health Stroke Scale [NIHSS]: 14.3). Favorable outcomes were reported in 76 patients (66.7%) in the MT-alone group and 42 patients (65.6%) in the com-bined group, with no significant between-group difference (P = 0.31 for noninferiority). However, MT alone was associated with a lower percentage of patients with successful reperfusion after MT compared with the combined group (87.7% vs. 90.6%). Mortality at 90 days was 12.2% (14 patients) in the MT-alone group and 17.2% (11 patients) in the combined group. The incidence of symptomatic intracerebral hemorrhage was not significantly different between groups (6 [5.3%] vs. 1 [1.6%]; P = 0.42).Among patients with AIS due to LVO in our study, MT alone was noninferior in terms of functional outcomes compared with MT preceded by the administration of intravenous alteplase within 4.5 hours after symptom onset.

This study is based on the current state of management and legal documents in Vietnam. The documents related to national borders and territories, documents signed by Vietnam, and international treaties to which Vietnam is a member. Administrative boundaries on the mainland have documents guiding the determination of administrative boundaries. The administrative boundary consists of the land part and the sea part. There is no record of defining administrative boundaries at sea. This study proposes a number of options for determining maritime boundaries (internal waters) for the coastal provinces of Vietnam. Administrative boundary records, maps, and national geographic databases are used to build the administrative boundary database. The research results provide suitable technical solutions to determine the maritime boundary, taking into account the morphological features of the coast. The administrative boundary database is fully built, legal, unified, and included in the management system. The administrative boundary database management system is centrally managed and is capable of providing information to organizations and individuals in need.

Cutting force is a vital parameter that affects product quality. Proper control of the cutting force helps optimize the production process as it improves productivity and product quality. This paper assesses the influence of machining parameters, such as alloy steel hardness and workpiece diameters, to cutting forces when external cylindrical grinding by experimental methods. The cutting force was measured using a workpiece shaft-mounted sensor with a balanced bridge-type resistor sensor. Steel for testing: 40Cr, 9CrSi, 65Mn, and W18Cr4V, which were heat-treated at three different hardness levels: 40, 50, and 60 HRC. The Taguchi method's experimental results show that the main parameters affecting cutting forces are: Feed rate of the grinding wheel Sd, cutting depth t, and hardness of workpiece material on the HRC scale. Since then, we built a mathematical model of the normal cutting force function Fn and tangent cutting force function Ft according to Sd, t, and HRC of 9CrSi steel then tested again with three steel types: 40Cr, 65Mn, and W18Cr4V for quite similar results. The cutting force is controlled through cutting parameters suitable for different hardness and workpiece material based on this model.

Addition of HER2-targeted agents to neoadjuvant chemotherapy has dramatically improved pathological complete response (pCR) rates in early stage Human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Still, up to 50% of patients have residual disease following treatment and biomarkers predictive of response are urgently needed. We performed spatial proteomic characterization using NanoString GeoMX Digital Spatial Profiling (DSP) of 122 samples from 57 HER2-positive breast tumors from the neoadjuvant TRIO-US B07 clinical trial (discovery cohort, n=28; validation cohort, n=29) sampled pre-treatment, after 14-21 days of HER2-targeted therapy and at surgery. In situ quantification of 40 tumor and immune proteins across multiple pancytokeratin-enriched regions per sample revealed that treatment results in decreased HER2 signaling and increased immune infiltration after several weeks of therapy. These changes were more dramatic in tumors that ultimately undergo pCR, and a classifier trained to predict pCR using on-treatment and pre-treatment DSP protein levels had a cross-validation mean Area Under the Receiver Operating Characteristics (AUROC) of 0.733 in the discovery cohort and validated in an independent cohort (AUROC = 0.725). Thus, we demonstrate robust stratification of sensitive tumors early during neoadjuvant HER2-targeted therapy using a multiplex spatial proteomic biomarker with implications for tailoring subsequent therapy.

Many host organisms live in polymicrobial environments and must respond to a diversity of pathogens. The degree to which host defences towards one pathogen species affect susceptibility to others is unclear. We used a panel of Caenorhabditis elegans nematode isolates to test for natural genetic variation in fitness costs of immune upregulation and pathogen damage, as well as for trade-offs in defence against two pathogen species, Staphylococcus aureus and Pseudomonas aeruginosa. We examined the fitness impacts of transient pathogen exposure (pathogen damage and immune upregulation) or exposure to heat-killed culture (immune upregulation only) by measuring host population sizes, which allowed us to simultaneously capture changes in reproductive output, developmental time and survival. We found significant decreases in population sizes for hosts exposed to live versus heat-killed S. aureus and found increased reproductive output after live P. aeruginosa exposure, compared with the corresponding heat-killed challenge. Nematode isolates with relatively higher population sizes after live P. aeruginosa infection produced fewer offspring after live S. aureus challenge. These findings reveal that wild C. elegans genotypes display a trade-off in defences against two distinct pathogen species that are evident in subsequent generations.

RNA interference (RNAi) is a powerful tool that is being increasingly utilized for crop protection against viruses, fungal pathogens, and insect pests. The non-transgenic approach of spray-induced gene silencing (SIGS), which relies on spray application of double-stranded RNA (dsRNA) to induce RNAi, has come to prominence due to its safety and environmental benefits in addition to its wide host range and high target specificity. However, along with promising results in recent studies, several factors limiting SIGS RNAi efficiency have been recognized in insects and plants. While sprayed dsRNA on the plant surface can produce a robust RNAi response in some chewing insects, plant uptake and systemic movement of dsRNA is required for delivery to many other target organisms. For example, pests such as sucking insects require the presence of dsRNA in vascular tissues, while many fungal pathogens are predominately located in internal plant tissues. Investigating the mechanisms by which sprayed dsRNA enters and moves through plant tissues and understanding the barriers that may hinder this process are essential for developing efficient ways to deliver dsRNA into plant systems. In this review, we assess current knowledge of the plant foliar and cellular uptake of dsRNA molecules. We will also identify major barriers to uptake, including leaf morphological features as well as environmental factors, and address methods to overcome these barriers.

Protective symbionts can defend hosts from parasites through several mechanisms, from direct interference to modulating host immunity, with subsequent effects on host and parasite fitness. While research on symbiont-mediated immune priming (SMIP) has focused on ecological impacts and agriculturally important organisms, the evolutionary implications of SMIP are less clear. Here, we review recent advances made in elucidating the ecological and molecular mechanisms by which SMIP occurs. We draw on current works to discuss the potential for this phenomenon to drive host, parasite, and symbiont evolution. We also suggest approaches that can be used to address questions regarding the impact of immune priming on host-microbe dynamics and population structures. Finally, due to the transient nature of some symbionts involved in SMIP, we discuss what it means to be a protective symbiont from ecological and evolutionary perspectives and how such interactions can affect long-term persistence of the symbiosis.

For patients with acute large vessel occlusion (ALVO) in the anterior circulation who are able to undergo mechani-cal thrombectomy (MTB) within 4.5 hours, the need for intravenous thrombolysis prior to the intervention remains unclear.Patients who were eligible for intravenous thrombolysis, who presented with ALVO in the anterior circulation, and who started MTB within 4.5 hours were matched at a 1:1 ratio to a thrombectomy alone group or to a bridging therapy group. Patients in the bridging therapy group were administered intravenous alteplase at a standard dose of 0.9 mg/kg. We evaluated the safety and efficacy of the throm-bectomy alone group compared with the bridging therapy group.From December 2020 to September 2021, 60 patients were recruited in the study and completed the trial. The baseline para-meters of patients were similar between the two groups. At the 90-day follow-up, 18 patients (60%) in the thrombectomy alone group versus 18 patients (60%) in the bridging therapy group achieved functional independence (odds ratio [OR]: 1, 95% confidence interval [CI], 0.36-2.81). The successful recanalization (Thrombolysis in Cerebral Infarction [TICI] grade 2b to 3) rates on final angiography were 90% and 86.7%, respectively (OR, 0.72, 95% CI, 0.15-3.55). No significant differences were found between the two groups in the occurrence of symptomatic intracranial hemorrhage or 90-day mortality.Our preliminary results did not show the superiority of thrombectomy alone versus standard bridging therapy in patients with ALVO in the anterior circulation who undergo MTB within 4.5 hours. A larger sample size and other randomized controlled trials remain necessary to validate these results.

Lithium cobalt oxide (LiCoO2), an example of nanoscale transition metal oxide and a widely commercialized cathode material in lithium ion batteries, has been shown to induce oxidative stress and generate intracellular reactive oxygen species (ROS) in model organisms. In this study, we aimed to understand the time-dependent roles of abiotic ROS generation and Co ions released in aqueous medium by LiCoO2 NPs, and examined the induced biological responses in model bacterium, B. subtilis upon exposure. We found that the redox-active LiCoO2 NPs produced abiotic ROS primarily through H2O2 generation when freshly suspended. Subsequently, the freshly-suspended LiCoO2 NPs induced additional DNA breakage, and changes in expression of oxidative stress genes in B. subtilis that could not be accounted for by the released Co ions alone. Notably, in 48 hour old LiCoO2 suspensions, H2O2 generation subsided while higher concentrations of Co ions were released. The biological responses in DNA damage and gene expression to the aged LiCoO2 NPs recapitulated those induced by the released Co ions. Our results demonstrated oxidative stress mechanisms for bacteria exposed to LiCoO2 NPs were mediated by the generation of distinct biotic and abiotic ROS species, which depended on the aqueous transformation state of the NPs. This study revealed the interdependent and dynamic nature of NP transformation and their biological consequences where the state of NPs resulted in distinct NP-specific mechanisms of oxidative injury. Our work highlights the need to capture the dynamic transformation of NPs that may activate the multiple routes of oxidative stress responses in cells.

Among high-valence metal oxides, LiCoO2 and related materials are of environmental importance because of the rapidly increasing use of these materials as cathodes in lithium ion batteries. Understanding the impact of these materials on aqueous environments relies on understanding their redox chemistry because Co release is dependent on oxidation state. Despite the critical role that redox chemistry plays in cellular homeostasis, the influence of specific biologically relevant electron transporters such as nicotinamide adenine dinucleotide (NADH) and glutathione (GSH) on the transformation of engineered nanoparticles has not been widely considered previously. Here we report an investigation of the interaction of LiCoO2 nanoparticles with NADH and GSH. Measurements of Co release using inductively coupled plasma-mass spectrometry (ICP-MS) show that exposing LiCoO2 nanoparticles to either NADH or GSH increases solubilization of cobalt, while corresponding spectroscopic measurements show that NADH is concurrently oxidized to NAD+. To demonstrate that these effects are a consequence of the high-valence Co(III) in LiCoO2 nanoparticles, we performed control experiments using Co(II)-containing Co(OH)2 and LiCoPO4, and dissolved Co2+/Li+ ions. Additional experiments using molecules of similar structure to NADH and GSH, but that are not reducing agents, confirm that these transformations are driven by redox reactions and not by chelation effects. Our data show that interaction of LiCoO2 with NADH and GSH induces the release of Co2+ ions and alters the redox state of these biologically important transporters. Observation of NADH binding to LiCoO2 using X-ray photoelectron spectroscopy (XPS) suggests a surface catalyzed reaction. The reciprocal reduction of LiCoO2 to enable release of Co2+ and corresponding oxidation of NADH and GSH as model redox-active biomolecules has implications for understanding the biological impacts of high-valence metal oxide nanomaterials.

A scheme of a membrane distillation unit with the possibility of using solar energy collectors has been proposed for treatment of water–salt solutions. This scheme has been tested in the Simulink (MATLAB) simulation environment using a seawater desalination process as a model system. Based on solar radiation data received in Vietnam, a distillation process has been simulated using a solar collector and an electric heater. Experimental approbation of the model has been carried out by the desalination of a NaCl solution by membrane distillation with a porous condenser. The calculated productivity of the modeled system agrees with the obtained experimental data. Simulation showed the possibility of reducing energy consumption by 61% in the process of desalination of an aqueous solution of NaCl using low-grade heat.

Reciprocal adaptation between hosts and symbionts can drive the maintenance of symbioses, resulting in coevolution and beneficial genotypic interactions. Consequently, hosts may experience decreased fitness when paired with nonsympatric partners compared to sympatric symbionts. However, coevolution does not preclude conflict-host and symbiont can act to advance their own fitness interests, which do not necessarily align with those of their partner. Despite coevolution's importance in extant symbioses, we know little about its role in shaping the origin of symbioses. Here, we tested the role of coevolution in establishing a novel association by experimentally (co)evolving a host with a protective bacterium under environmental stress. Although evolution in the presence of nonevolving bacteria facilitated host adaptation, co-passaged hosts did not exhibit greater adaptation rates than hosts paired with nonevolving bacteria. Furthermore, co-passaged hosts exhibited greater fecundity when paired with sympatric, co-passaged bacteria compared to co-passaged bacteria with which they did not share an evolutionary history. Thus, shared evolutionary history between the hosts and microbes actually reduced host fitness and has the potential to impede evolution of new beneficial associations.

Background The incidence of antimicrobial-resistant Neisseria gonorrhoeae (GC) is rising in Canada; however, antimicrobial resistance (AMR) surveillance data are unavailable for infections diagnosed directly from clinical specimens by nucleic acid amplification tests (NAATs), representing over 80% of diagnoses. We developed a set of 10 improved molecular assays for surveillance of GC-AMR and prediction of susceptibilities in NAAT specimens. Methods Multiplex real-time PCR (RT–PCR) assays were developed to detect SNPs associated with cephalosporin (ponA, porB, mtrR −35delA, penA A311V, penA A501, N513Y, G545S), ciprofloxacin (gyrA S91, parC D86/S87/S88) and azithromycin [23S (A2059G, C2611T), mtrR meningitidis-like promoter] resistance. The assays were validated on 127 gonococcal isolates, 51 non-gonococcal isolates and 50 NAATs with matched culture isolates. SNPs determined from the assay were compared with SNPs determined from in silico analysis of WGS data. MICs were determined for culture isolates using the agar dilution method. Results SNP analysis of the 50 NAAT specimens had 96% agreement with the matched culture RT–PCR analysis. When compared with MICs, presence of penA A311V or penA A501 and two or more other SNPs correlated with decreased susceptibility and presence of three or more other SNPs correlated with intermediate susceptibility to cephalosporins; presence of any associated SNP correlated with ciprofloxacin or azithromycin resistance. NAAT-AMR predictions correlated with matched-culture cephalosporin, ciprofloxacin and azithromycin MICs at 94%, 100% and 98%, respectively. Conclusions We expanded molecular tests for N. gonorrhoeae AMR prediction by adding new loci and multiplexing reactions to improve surveillance where culture isolates are unavailable.

Background: While introduction of HER2-targeted therapies has dramatically improved outcomes for patients with HER2-positive disease, even with the addition of HER2-targeted agents, 40-50% of patients do not achieve a pCR (pathologic complete response) following neoadjuvant therapy implying that clinical or molecular differences may be present in responders versus non-responders. While recent bulk expression studies have identified several biomarkers associated with response to HER2-targeted therapies in the neoadjuvant setting, these studies are limited in their ability to assign observed changes to specific geographic or phenotypic cell populations, such as the malignant tumor core or the surrounding microenvironment. Methods: Here we used the Digital Spatial Profiler (DSP, NanoString Technologies, Inc.) to profile regions-of-interest containing pancytokeratin (panCK)+ tumor cells and infiltrated immune cells that are co-localized with the tumor cells. Using this technology, we assayed archival tissue from 28 patients with HER2-positive breast cancer from the TRIO-B07 (NCT00769470) clinical trial, who were treated with trastuzumab, lapatinib, or both, followed by standard chemotherapy plus HER2-targeted therapy. Tissue specimens were collected from the pre-treatment diagnostic biopsy (Baseline) and after one cycle of targeted therapy (Runin). To study regional heterogeneity, we selected an average of four panCK-enriched tissue regions from each sample. Using DSP, we performed multiplexed quantification of 38 tumor and immune protein markers and 96 RNA markers on the selected tissue regions and compared our findings to bulk mRNA expression data from the same cohort. Results: Within the panCK-enriched regions, DSP revealed significant treatment-associated decreases in HER2 protein levels and the downstream PI3K-Akt signaling pathway in Runin compared to Baseline samples. In tandem, we observed a significant increase in infiltrating leukocytes, with CD45, a pan-leukocyte marker, and CD8, a marker for T cells that mediate tumor cell killing, showing the most dramatic changes. These changes in Runin compared to Baseline were more significant in the subset of cases that achieved a pCR versus those that do not, independent of ER status. Comparison of Runin samples to matched Baseline samples from the same patient enabled improved prediction of patient outcome (pCR) compared with analysis of a single timepoint alone. We also found that the DSP panCK enrichment strategy captures additional signal not observed in bulk expression data. For instance, using bulk expression, a decrease in HER2 RNA levels between Baseline and Runin was evident but there was no difference in the degree of decrease in HER2 mRNA between pCR and no pCR cases. Using DSP, we observed that the significant decrease in HER2 levels at Runin is more pronounced in cases that achieved a pCR. Across both tumor and immune markers, regional heterogeneity increased at Runin compared to Baseline. Conclusions: In this study, we used DSP and a panCK enrichment strategy to retrospectively delineate the changes that occurred in tumor cells and co-localized immune cells during HER2-targeted therapy. In comparison to traditional or multiplexed IHC, DSP allows for simultaneous profiling of a large number of markers, enabling the characterization of multiple cancer signaling pathways and immune markers on a single tissue specimen. This study demonstrates the utility of pancytokeratin-enriched spatial proteomic profiling to characterize treatment-associated changes and identify predictive biomarkers. NanoString’s Digital Spatial Profiler is for Research Use Only. Not to be used for diagnostic procedures. Citation Format: Katherine Lee McNamara, Jennifer L. Caswell-Jin, Zhicheng Ma, Jason J. Zoeller, Michelle Kriner, Zoey Zhou, Jason Reeves, Margaret Hoang, Joseph Beechem, Dennis J. Slamon, Michael F. Press, Joan Brugge, Sara A. Hurvitz, Christina Curtis. Characterizing the tumor and immune microenvironment through treatment to predict response to neoadjuvant HER2-targeted therapy using the Digital Spatial Profiler [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-10-12.

Hydrazones readily synthesized from N-aminopyrroles or N-aminoazoles and aldehydes undergo Rh(III)-catalyzed dual C-H activation and coupling with aryl- and alkyl-substituted alkynes to give pyrrolopyridazines or azolopyridazines, respectively. This transformation represents a rare example of hydrazoyl C-H activation and proceeds without heteroatom functionality to direct C-H activation. Hydrazones derived from aromatic, alkenyl, and aliphatic aldehydes were effective inputs, and tethering the alkyne to the hydrazone enabled annulations to more complex, tricyclic products.

The Spatial Molecular Imaging platform (CosMxTM SMI, NanoString Technologies, Seattle, WA) utilizes high-plex in-situ imaging chemistry for both RNA and protein detection. This automated instrument provides 1000’s of plex, at high sensitivity (1 to 2 copies/cell), very low error rate (0.0092 false calls/cell) and background (∼0.04 counts/cell). The imaging system generates three-dimensional super-resolution localization of analytes at ∼2 million cells per sample, four samples per run. Cell segmentation is morphology-based using antibodies, compatible with FFPE samples. Multiomic data (980 RNAs, 108 proteins) were measured at subcellular resolution using FFPE tissues (non-small cell lung (NSCLC) and breast cancer) and allowed identification of over 18 distinct cell types, 10 unique tumor microenvironments, and 100 pairwise ligand-receptor interactions. Over 800,000 single cells and ∼260 million transcripts data are released into the public domain allowing extended data analysis by the entire spatial biology research community.