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Artificial van der Waals heterostructures, obtained by stacking layered two-dimensional materials, represent a novel material platform for investigating physicochemical phenomena and applications. We report here electrochemistry at the one-dimensional edge of a graphene sheet, which is sandwiched between two hexagonal boron nitride (hBN) multilayer flakes. When such an hBN/graphene/hBN heterostructure is immersed in a solution, the basal plane of graphene is protected and isolated by the hBN stack, and the edge of the graphene sheet is exclusively available in the solution. This forms an electrochemical nanoelectrode, which enabled us to investigate electron transfer using several redox probes, e.g., ferrocene(di)methanol, hexaammineruthenium, methylene blue, dopamine and ferrocyanide. Facilitated by the relatively low capacitance of the van der Waals edge electrode, we demonstrate cyclic voltammetry at very high scan rates (up to 1000 V/s). Using fast scan cyclic voltammetry imaging, we show that redox species can be detected voltammetrically down to micromolar concentrations with subsecond time resolution at the sandwiched graphene edge, promoted by the rapid equilibration of analyte species in the diffusion layer. Furthermore, the nanoband nature of the edge electrode allows us to work directly in water in the absence of added electrolyte. Finally, we show that two adjacent edge electrodes can be realized in a redox-cycling format. In all, the van der Waals edge electrode is unique among nanoelectrodes as it enables investigations of all the above-mentioned phenomena in the same device. Due to its versatility, it constitutes a new avenue for nanoscale electrochemistry, which will be useful for studying electron transfer mechanisms as well as for the detection of analyte species in ultralow sample volumes.

Supplementary Materials and Methods. Supplementary Figures: Fig. S1. Sorting strategy and purity. Fig. S2. Comparison of the two batches of NanoString experiments shown in Fig. 1 and Fig. 4. Fig. S3. Melanoma cells respond to CTL attack with gene expression changes. Fig. S4. CTL-induced gene expression changes are driven by IFNgamma and TNFalpha. Fig. S5. Representative histograms of protein expression regulated by cytokines. Fig. S6. Characterization of untreated and CTL-exposed melanocytes. Supplementary Tables: Table S1. Source of the 17 melanoma cell lines used in this study. Table S2. Antibodies (including isotype-matched controls) used to assess protein expression by flow cytometry. Table S3. Differential expression of genes that are part of the enriched gene sets in Supplementary Figs. S3C and S3E. Table S4. Selection of genes for 181-gene panel. Table S5. Differential expression of genes in melanoma cell lines after 24h treatment. Table S6. Protein expression of melanoma cells after 48h culture in presence or absence of IFNgamma and TNFalpha. Table S7. Differential expression of genes in melanocyte cell lines after 24h treatment. Table S8. Genes that have statistically different fold-changes (MelanA-specific CTLs/untreated) between melanoma cell lines and melanocyte lines. Supplementary References.

Although mutations drive cancer, it is less clear to what extent genetic defects control immune mechanisms and confer resistance to T-cell-based immunotherapy. Here, we studied the reactions of malignant and benign melanocyte lines to cytotoxic CD8+ T cells (CTL) using flow cytometry and gene expression analyses. We found rapid and broad upregulation of immune-regulatory genes, essentially triggered by CTL-derived IFNγ and augmented by TNFα. These reactions were predominantly homogenous, independent of oncogenic driver mutations, and similar in benign and malignant cells. The reactions exhibited both pro- and antitumorigenic potential and primarily corresponded to mechanisms that were conserved, rather than acquired, by mutations. Similar results were obtained from direct ex vivo analysis of the tumor microenvironment. Thus, immune regulation in the tumor landscape may often be driven by conserved mechanisms, which may explain why T-cell–based immunotherapy can provide durable benefits with relatively infrequent escape. Cancer Res; 77(7); 1623–36. ©2017 AACR.

Managers and ministers exercise influence over their members inside and outside of their organizations. We examine the relationship of servant leadership from two contexts, an individual's workplace and place of worship, with regulatory foci, and, in turn, entrepreneurial behavior and counterproductive work behavior (CWB) at work. Moreover, we contend that spiritual discipline (i.e., prayer and reading sacred texts) moderates the relationship of servant leadership to regulatory focus by altering the salience of each leader's behavior. Using data collected in two waves from 912 working adults, we test the proposed relationships with multi-group structural equation modeling. Findings largely support the hypotheses and point toward important implications for servant leadership in both workplace and place of worship settings.

N,N-dimethyldithiocarbamate (DMDC) is a potent copper-dependent antimicrobial against several pathogens, including Streptococcus pneumoniae. Despite the availability of several vaccines against multiple disease-causing strains of S. pneumoniae, the rise of antimicrobial resistance and pneumococcal disease caused by strains not covered by the vaccine creates a need for developing novel antimicrobial strategies. We derived novel compounds from DMDC and tested their effectiveness as copper-dependent antimicrobials against S. pneumoniae through in vitro growth and killing curves. Compounds that caused a growth defect and were bactericidal in vitro were tested against other strains of S. pneumoniae and in complex with different transition metals. We found two compounds, sodium N-benzyl-N-methyldithiocarbamate and sodium N-allyl-N-methyldithiocarbamate (herein “Compound 3” and “Compound 4”), were effective against TIGR4, D39, and ATCC® 6303™ (a type 3 capsular strain) and further increased the internal concentrations of copper to the same previously reported levels as with DMDC and copper treatment. We found that both Compound 3 and Compound 4 were bacteriostatic in combination with zinc. We tested Compound 3 and Compound 4 in vivo against a murine pneumonia model, finding that Compound 3, and not Compound 4, was effective in significantly decreasing the bacterial burden in the blood and lungs of S. pneumoniae-infected mice. We found that the combination of Compound 3 and copper made the pneumococcus more susceptible to activated macrophage mediated killing via an in vitro macrophage killing assay. Collectively, we demonstrate that derivatizing DMDC holds promise as potent bactericidal antibiotics against S. pneumoniae.

Persistent and pervasive rudeness and lack of respect are unfortunately common in workplaces today. The deleterious effects of this incivility at work may be even worse than previously demonstrated, impacting not only employee victims but also trickling down to those who employees contact. However, we propose that leaders who prioritize their followers’ needs above their own, also known as servant leaders, may be a critical preventative mechanism to reduce group-level incivility through promoting a virtuous climate. Applying social learning theory and social information processing theory, we argue that servant leaders role model virtuous character that contributes to a virtuous climate that influences group members to reduce incivility and, in turn, treat others well. We utilize the healthcare setting (1,485 nurses in 71 hospital units) to support this hypothesized process across multi-source measures of incivility from coworkers and team supervisors and three indicators of quality of patient care. Specific findings and implications for managers in healthcare settings and beyond are discussed.

Streptococcus pneumoniae is a Gram-positive, encapsulated bacterium that is a significant cause of disease burden in pediatric and elderly populations. The rise in unencapsulated disease-causing strains and antimicrobial resistance in S. pneumoniae has increased the need for developing new antimicrobial strategies.

We present here the electrochemistry at a photolithographically created isolated monolayer graphene edge (GrEdge). The millimeter-long GrEdge is found to behave like a nanowire, exhibiting very hig...

Servant leadership is a model of leadership based on ethics and benevolent service to others and has been associated with numerous positive outcomes for employees and organizations. Due to a limited number of studies examining servant leadership (SL) within sport, the purpose of this study was to investigate the relation of servant leadership and leader effectiveness outcomes in sport administration and to examine if political skill (i.e., how people influence others), was a moderator of servant leader effectiveness. A multilevel model was used to examine these questions within a sample of interscholastic athletic directors and head coaches. Findings revealed servant leadership was directly related to leader effectiveness (LE), affective organizational commitment (AOC), and job satisfaction (JS) of head coaches. Moreover, there was a significant negative interaction between servant leadership and political skill. The negative interaction may indicate that extreme values of servant leadership have opposite relations to leader effectiveness and other outcomes when political skill is present. Though a minimal effect, political skill detracts from LE in those who are perceived as exhibiting strong servant leader behaviors. Findings and limitations are discussed; questions for future research are suggested.

Practitioners are seeking information and ethical guidance related to the design and utilization of artificial intelligence (AI) across a variety of applications. Developments at Google illustrate the potential good of AI as well as potential concerns. In this article, we use Google to create a context that demonstrates the relevance of virtue for the ethical design and use of AI. We describe a set of ethical challenges encountered by Google and introduce virtue as a framework for ethical decision making that can be applied broadly to numerous organizations. We also examine support for virtue in ethical decision making as well as its power in attracting and retaining the employees who develop AI and the customers who use it. To conclude, we apply the virtue framework to Google’s AI challenges and offer suggestions for its use in other organizations.

Achieving long term stability of single graphene sheets towards repeated electrochemical hydrogen evolution reaction (HER) cycling has been challenging. Here, we show through appropriate electrode preparation that it is possible to obtain highly durable isolated graphene electrodes, which can survive several hundreds of HER cycles with virtually no damage to the sp

Electrochemical hydrogen evolution reaction (HER) at single graphene sheets has been investigated widely either in its pristine form or after chemical modification. One important challenge is the long-term stability of single graphene sheets on Si/SiO2 substrates under HER. Previous reports have found that due to stress developing under gas evolution, the sheets tend to break apart, with a very low lifetime limited to just a few cycles of HER. Here, we show through appropriate electrode preparation that it is possible to achieve highly durable single graphene electrodes on insulating substrates, which can survive several hundreds of HER cycles with virtually no damage to the sp2-carbon framework. Through systematic investigations including atomic force microscopy, Raman spectroscopy and electroanalysis, we show that even after so many cycles, the sheet is physically intact and the electron transfer capability of the electrodes remain unaffected. This extremely high stability of a single atomic sheet of carbon, when combined with appropriate chemical modification strategies, will pave way for the realization of novel 2D electrocatalysts.

Transition metals are necessary cofactors and structural elements in living systems. Exposure to high concentrations of biologically important transition metals, such as zinc and copper, results in cell toxicity. At the infection site, the immune system deploys metal sorbent proteins (e.g., lactoferrin and calprotectin) to starve pathogens of necessary metals (such as iron), while phagocytes expose engulfed pathogens to high levels of other metals, such as copper and zinc. The opportunistic pathogen Streptococcus pneumoniae (the pneumococcus) encounters macrophages during initial and protracted infections. The pneumococcus employs a copper export pathway, which improves colonization and persistent infection of the nasopharynx and the upper respiratory tract. Because copper is tightly regulated in the host, we instead sought to leverage the localized power of nutritional immunity by identifying small molecules with copper-dependent toxicity (CDT) through a targeted screen of compounds for antibiotic efficacy. We chose to include dithiocarbamates, based on the copper synergy observed in other organisms with 1-(diethylthiocarbamoyldisulfanyl)-N,N-diethyl-methanethioamide (tetraethylthiuram disulfide, disulfiram). We observed CDT of some dithiocarbamates in S. pneumoniae. Only N,N-dimethyldithiocarbamate (DMDC) was consistently toxic across a range of concentrations with copper both in vitro and in vivo against the pneumococcus. We also observed various degrees of CDT in vitro using DMDC in Staphylococcus aureus, Coccidioides posadasii, and Schistosoma mansoni. Collectively, we demonstrate that the compound DMDC is a potent bactericidal compound against S. pneumoniae with antimicrobial efficacy against bacterial and fungal pathogens. IMPORTANCE With the rise of antibiotic resistance, approaches that add new antimicrobials to the current repertoire are vital. Here, we investigate putative and known copper ionophores in an attempt to intoxicate bacteria and use ionophore/copper synergy, and we ultimately find success with N,N-dimethyldithiocarbamate (DMDC). We show that DMDC has in vitro efficacy in a copper-dependent manner and kills pathogens across three different kingdoms, Streptococcus pneumoniae, Coccidioides posadasii, and Schistosoma mansoni, and in vivo efficacy against S. pneumoniae. As such, dithiocarbamates represent a new potential class of antimicrobials and thus warrant further mechanistic investigation.

Nanotechnology is a recent development within construction, however, exposure to nanomaterials entails exposure to emerging hazards and risk, which is exacerbated by the limited knowledge pertaining thereto. A quantitative survey was conducted among medium to large sized general contractors, and architects in the Eastern Cape province, South Africa. The salient findings include: architects and contractors specify and use nanomaterials during the construction process; architects follow ‘designing for safety’ practice to a limited extent; contractors conduct the necessary training, inform their employees of the potential hazards related to the use of nanomaterials, implement safe application techniques when working with nanomaterials, issue employees with the necessary PPE to carry out the work safely, and generally do not analyse the characteristics of materials to a major extent, but do analyse material safety data sheets (MSDSs). Conclusions include: there is a low level of awareness and knowledge with respect to nanomaterials; the responding architects are barely committed to construction H&S; responding contractors are committed to H&S, and there is a need for research to determine the healthiest and safest methods of using nanomaterials. It is recommended that designers and contractors should enhance their awareness of and knowledge pertaining to nanomaterials, including the hazards and risks.

This is the first paper in the symposium Faith in Management Scholarship and Practice. In this role it lays out how a set of naturalistic and materialistic assumptions can be limiting for scholarsh...

Immunotherapies against cancer continue to improve, but many cancers show primary or secondary resistance. Novel research strategies are necessary to reach a comprehensive understanding of the underlying mechanisms. There is increasing evidence that T cells themselves provoke immune escape of cancer cells. In this chapter we describe a co-culture system to analyze the dynamic interplay between T cells and cancer cells. Using human melanoma cell lines and T cell clones, we obtained reproducible and comparable results despite the high heterogeneity of tumor cells. We show the feasibility of differential protein and gene expression analysis of melanoma cells isolated from our culture system. Thus, the system allows quantifying broadly the differential gene expression in melanoma cells upon interaction with T cells, revealing immune-related reactions in cancer cells. Many parts of this chapter were previously published in an original paper and are reproduced here for this book.

Immunotherapies against cancer continue to improve, but many cancers show primary or secondary resistance. Novel research strategies are necessary to reach a comprehensive understanding of the underlying mechanisms. There is increasing evidence that T cells themselves provoke immune escape of cancer cells. In this chapter we describe a co-culture system to analyze the dynamic interplay between T cells and cancer cells. Using human melanoma cell lines and T cell clones, we obtained reproducible and comparable results despite the high heterogeneity of tumor cells. We show the feasibility of differential protein and gene expression analysis of melanoma cells isolated from our culture system. Thus, the system allows quantifying broadly the differential gene expression in melanoma cells upon interaction with T cells, revealing immune-related reactions in cancer cells. Many parts of this chapter were previously published in an original paper and are reproduced here for this book.

Servant leadership is ripe for exploration from both etic and emic perspectives investigating its robustness as a leadership style globally. Through a meta-analysis of data from 139 studies, we examine the relationship of servant leadership with 23 attitudinal, behavioral, and performance outcomes across cultures. Utilizing values and practices approaches to culture, we test the moderating influence of a profile of four GLOBE culture dimensions theoretically linked to servant leadership: assertiveness, institutional collectivism, humane orientation, and power distance. The findings provide evidence of servant leadership's association with workplace outcomes, grant insight into contingencies of cultural practices and values, and offer directions for future research.

This study investigates the relationship between an organization’s religious values, as espoused by the founder or in media messaging, and applicant intentions to pursue a job. Drawing on person-organization fit theory, we also explored interactions between an organization’s espoused religious values and characteristics of the individual applicant. We tested our predictions via two conjoint analysis experiments, one with 191 employed adults collectively making 2292 employment pursuit decisions and a second with 120 employed adults making 1080 employment pursuit decisions. Espousing religious values as a founder or in media messaging yielded lower intentions to pursue a job than when an organization espouses non-religious values. However, when there was fit based on religious values, these relationships were mitigated. The results expand our understanding of person-organization fit by demonstrating the potential influence of espousing religious values on attracting organizational members.

Servant leadership is a style of leadership characterized by principles of other-centeredness and ethical behavior, and suggests that truly effective and legitimate leaders place service to others ahead of personal power and control. Studies on servant leadership in organizational and sport settings have consistently produced positive outcomes. However, the idea of servant leadership as a model for successful leadership in sport is only in the early stages of being accepted. Motivated by a need for adequate information and pedagogical resources, the present review describes the origin and conceptualization of servant leadership and summarizes the positive outcomes resulting from servant leadership. A model for understanding servant-leadership attributes and dynamics is presented along with recommendations for sport management educators.

The emergence and scope of personal and collective efforts to integrate faith into workplaces is a social movement that includes and extends beyond personal ethics. This paper discusses the development of The Integration Profile (TIP) Faith and Work Integration Scale, which is designed to measure the multidimensional nature of faith expressions within workplace settings. TIP measures the manifestations of faith, religion, and spirituality at the individual level. Earlier research theorized that individuals tend to manifest or live out their faith in one of four ways (Miller in God at work: the history and promise of the faith at work movement, Oxford University Press, New York, 2007); TIP expands this to assess eight sub-orientations, nested within the four main manifestations of faith–work integration. The development of the 24-item TIP scale involved exploratory analyses in a sample of 512 employees of a for-profit palliative care organization and a hierarchical confirmatory factor analysis in a sample of 4463 employees in an American multinational food processing organization. Additional analyses were conducted in a third sample of 266 working adults to assess the convergent and discriminant validity of the eight sub-orientations with other faith variables as well as associations with work outcomes.

Electrografting of gold and graphene surfaces by functional p‐(N‐maleimido)phenyl groups was performed by reduction of p‐(N‐maleimido)phenyldiazonium tetrafluoroborate. The reduction was carried out using cyclic voltammetry coupled with micro-gravimetric measurements by means of electrochemical quartz crystal microbalance (EQCM). The overall deposited mass on gold was higher than on graphene. However, the Faradaic efficiency was lower on Au (14%) compared to graphene (22%) after the first potential scan. Subsequently, the maleimide functional groups have been tested for immobilization of terminal thiols using (4-nitrobenzyl)mercaptan for the functionalized graphene surface and a cysteine-modified peptide for the functionalized gold surface. The functionalization by p‐(N‐maleimido)phenyl groups and the following thiol coupling of the particular surface was proven by infrared spectroscopic ellipsometry (IRSE). In addition, the interaction of the tetrabutylammonium and tetrafluoroborate ions present in the electrolyte with the Au and graphene electrodes was investigated by EQCM and revealed less electrostatic interaction of graphene with these ions in solution compared to the metal (Au) surface.

Although mutations drive cancer, it is less clear to what extent genetic defects control immune mechanisms and confer resistance to T-cell-based immunotherapy. Here, we studied the reactions of malignant and benign melanocyte lines to cytotoxic CD8+ T cells (CTL) using flow cytometry and gene expression analyses. We found rapid and broad upregulation of immune-regulatory genes, essentially triggered by CTL-derived IFNγ and augmented by TNFα. These reactions were predominantly homogenous, independent of oncogenic driver mutations, and similar in benign and malignant cells. The reactions exhibited both pro- and antitumorigenic potential and primarily corresponded to mechanisms that were conserved, rather than acquired, by mutations. Similar results were obtained from direct ex vivo analysis of the tumor microenvironment. Thus, immune regulation in the tumor landscape may often be driven by conserved mechanisms, which may explain why T-cell–based immunotherapy can provide durable benefits with relatively infrequent escape. Cancer Res; 77(7); 1623–36. ©2017 AACR.

Regulatory focus as a motivational mechanism, plays a significant role in determining whether leaders and followers will focus on promotion goals, aspiring to “keep their head in the clouds” thinki...

Electrochemical devices based on a single graphene monolayer are often realized on a solid support such as silicon oxide, glassy carbon or a metal film. Here, we show that, with graphene on insulating substrates, the kinetics of the electron transfer at graphene with various redox active molecules is dictated by solution pH for electrode reactions that are not proton dependent. We attribute the origin of this unusual phenomenon mainly to electrostatic effects between dissolved/dissociated redox species and the interfacial charge due to trace amounts of ionizable groups at the supported graphene–liquid interface. Cationic redox species show higher electron transfer rates at basic pH, while anionic species undergo faster electron transfer at acidic pH. Although this behavior is observed on graphene on three different insulating substrates, the strength of this effect appears to differ depending on the surface charge density of the underlying substrate. This finding has important implications for the design of electrochemical sensors and electrocatalysts based on graphene monolayers.

We report the direct exclusive modification of the edge of a single graphene monolayer with nanoparticles or organic functionalities under ambient conditions., We present a versatile and simple method using electrochemistry for the exclusive functionalization of the edge of a graphene monolayer with metal nanoparticles or polymeric amino groups. The attachment of metal nanoparticles allows us to exploit surface-enhanced Raman scattering to characterize the chemistry of both the pristine and the functionalized graphene edge. For the pristine patterned graphene edge, we observe the typical edge-related modes, while for the functionalized graphene edge we identify the chemical structure of the functional layer by vibrational fingerprinting. The ability to obtain single selectively functionalized graphene edges routinely on an insulating substrate opens an avenue for exploring the effect of edge chemistry on graphene properties systematically.

Correction for ‘pH sensitivity of interfacial electron transfer at a supported graphene monolayer’ by Michel Wehrhold et al., Nanoscale, 2019, DOI: 10.1039/c9nr05049c.

Accumulating evidence finds servant leadership is related to critical employee and organizational criteria, but only a limited amount of studies link servant leaders to both internal and external stakeholder outcomes. Moreover, there remains a great deal to learn regarding the conditions under which this influence is enhanced or diminished. We address these limitations in the literature by testing a multilevel model that hypothesizes servant leadership is related to nurse behavior and satisfaction as well as patient satisfaction. Further, drawing upon contingency theory, we test a contextual moderator, organizational structure, as a potential enhancer of the relationships between servant leadership and these outcomes. Using a sample of 1485 staff nurses and 105 nurse managers at nine hospitals, we demonstrated that servant leadership is directly related to more nurse helping and creative behavior, and it is related to patient satisfaction through nurse job satisfaction. Also, organizational structure acted as a moderator to enhance the influence of servant leadership on creative behavior as well as patient satisfaction through nurse job satisfaction. Limitations and future research directions are discussed.

Monoclonal antibody-based targeted tumor therapy has greatly improved treatment options for patients. Antibodies against oncogenic receptor tyrosine kinases (RTKs), especially the ErbB receptor family, are prominent examples. However, long-term efficacy of such antibodies is limited by resistance mechanisms. Tumor evasion by a priori or acquired activation of other kinases is often causative for this phenomenon. These findings led to an increasing number of combination approaches either within a protein family, e.g. the ErbB family or by targeting RTKs of different phylogenetic origin like HER1 and cMet or HER1 and IGF1R. Progress in antibody engineering technology enabled generation of clinical grade bispecific antibodies (BsAbs) to design drugs inherently addressing such resistance mechanisms. Limited data are available on multi-specific antibodies targeting three or more RTKs. In the present study, we have evaluated the cloning, eukaryotic expression and purification of tetraspecific, tetravalent Fc-containing antibodies targeting HER3, cMet, HER1 and IGF1R. The antibodies are based on the combination of single-chain Fab and Fv fragments in an IgG1 antibody format enhanced by the knob-into-hole technology. They are non-agonistic and inhibit tumor cell growth comparable to the combination of four parental antibodies. Importantly, TetraMabs show improved apoptosis induction and tumor growth inhibition over individual monospecific or BsAbs in cellular assays. In addition, a mimicry assay to reflect heterogeneous expression of antigens in a tumor mass was established. With this novel in vitro assay, we can demonstrate the superiority of a tetraspecific antibody to bispecific tumor antigen-binding antibodies in early pre-clinical development.