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•CD14+monocytes from patients with CH stimulate inflammation through increased cytokine expression.•T cells from CH are deficient in GIMAP expression, suggesting CH may impair T-cell differentiation.

As e‐commerce emerges as a central mechanism through which customers make purchases, so does the diversity of products they choose to purchase online. One of the fastest‐growing product categories is that of large and oversized items, often referred to as “big and bulky” items. This trend is particularly pronounced in the United States, with the online appliance and furniture markets experiencing substantial growth. Significant growth is also observed in the last‐mile delivery services sector for these large items. This presents a plethora of opportunities for industry stakeholders. Capitalizing on these opportunities and achieving service differentiation requires significant strategic investments in specialized equipment and capabilities by retailers and logistics service providers. These capabilities differ significantly from those typically required to deliver standard consumer products. This shift in operational context requires a deep understanding of customer preferences regarding big and bulky item delivery services. In this study, we determine customer preferences for big and bulky item delivery service features and quantify the effect of customer psychographic traits on those preferences. We accomplish this by conducting a choice‐based conjoint experiment. Our findings indicate significant effects that bear both research and managerial implications.

As developed markets become more saturated, managers increasingly recognize the value of emerging markets as venues for growth opportunities. Yet, launching products into these markets is extremely risky due to weak institutional environments (e.g., lack of physical infrastructure), making success more uncertain. To alleviate this challenge, theory points to using emerging market footholds that yield market‐specific knowledge. However, it is unclear whether knowledge is realized and, if so, what facets of harvested knowledge are effective in driving performance. Accordingly, we used data collected from a survey of business professionals to examine emerging market footholds and market‐specific knowledge (i.e., customer, competitor, and logistics knowledge). Our results show that the extent of market presence held by an emerging market foothold is positively associated with all types of knowledge, yet only competitor and logistics knowledge—not customer knowledge—is positively associated with product launch performance. A supplemental sample of new product launches in developed markets revealed the opposite results wherein customer knowledge was the only significant predictor. Viewed collectively, the results suggest a market maturity threshold wherein logistics and competitive knowledge becomes less influential in driving performance, and customer knowledge becomes more influential.

Loss of function mutations in TET2are common in clonal hematopoiesis (CH) and myelodysplastic syndromes (MDS). Increased inflammation and stem cell capacity have been reported in Tet2 KOmouse models, but molecular mechanisms and cell type-specific contributions to explain this phenotype are lacking. To create models of CH-like TET2 deficiency, we transplanted Mx1-CRE Tet2 fl/fl(Tet2 KO)or Tet2 fl/fl(both CD45.1 +)in CD45.2 +recipientsfollowing radiation-free conditioning with ACK2 (anti-cKit) antibody injection. Six months post-transplant, we flow sorted CD45.1 +Tet2 KOand Tet2 fl/flLin -Sca-1 +cKit +(LSK) cells, granulocyte-monocyte progenitors (GMP), and monocytes for RNA and assay for transposase-accessible chromatin (ATAC) sequencing. Differential gene expression analysis identified 902 (468 up, 434 down) differentially expressed genes (DEGs) in LSK, 134 (95 up, 39 down) in GMP, and 474 (125 up, 349 down) in monocytes (p adj<0.05). Gene set enrichment analysis (GSEA) identified that the top Hallmark gene sets in Tet2 KOLSK cells were related to MYC targets, oxidative phosphorylation, and E2F targets. In contrast, GMP and monocytes were most enriched for IFN-alpha and gamma gene sets along with IL6/JAK/STAT3 signaling. ATACseq revealed increased accessibility of myeloid-related transcription factor (TF) binding motifs in Tet2 KOLSK cells (CEBPA, PU.1-IRF(ETS:IRF), and AP-1 TF FOSL2(bZIP)), while prediction of cis-regulating regions via GREAT identified downregulated peaks associated with stem cell maintenance and upregulated peaks associated with myeloid mediated immunity. Peaks upregulated in Tet2 KOGMP cells were enriched for the motifs recognized by CEBPE, ISRE(IRF)) and the AP-1 TF JUND, while upregulated peaks in monocytes were enriched for RUNX1 and CEBPA motifs, as well as AP-1 TF FOS::JUNB. GREAT analysis in GMPs identified cis-regulatory regions related to myeloid mediated immunity, while monocytes possessed those associated with biotic stimuli.

Herein, we report the discovery of a new, orally bioavailable and CNS-penetrant metabotropic glutamate receptor 7 (mGlu7) negative allosteric modulator (NAM) that achieves exposure in cerebral spinal fluid (CSF) 2.5× above the in vitro IC50at minimum effective doses (MEDs) of 3 mg/kg in preclinical anxiety models.

Management of volunteer horseradish is a challenge when it is grown in rotation with other crops, such as corn and soybean. Although volunteer horseradish may not cause yield loss, these plants serve as hosts for various soilborne pathogens that damage subsequent horseradish crops. In addition to volunteer horseradish, glyphosate-resistant Palmer amaranth is becoming difficult to control in southwestern Illinois, as a consequence of the plant’s ability to withstand glyphosate and drought, produce many seeds, and grow rapidly. Field studies were conducted to evaluate the effect of glyphosate and dicamba on volunteer horseradish and Palmer amaranth control in 2014 and 2015. Glyphosate alone (1,265 and 1,893 g ae ha-1) and glyphosate plus dicamba at the high rate (1,680 g ae ha-1) provided the greatest volunteer horseradish control, ranging from 81% to 89% and 90% to 93%, respectively. Measures of root biomass reduction followed similar trends. Glyphosate alone provided the greatest reduction in volunteer horseradish root viability (79% to 100%) but was similar in efficacy to applications of glyphosate plus dicamba in most comparisons. Efficacy of PRE-only applications on Palmer amaranth control ranged from 92% to 99% control in 2014 and 68% to 99% in 2015. However, PRE-only applications were often similar in efficacy to PRE followed by (fb) glyphosate plus dicamba applied POST. Treatments containing flumioxazin did not control Palmer amaranth as well as other treatments. POST applications alone were not effective in managing Palmer amaranth. Many of the PRE fb POST treatment options tested will improve resistance management over PRE-only treatments, provide control of Palmer amaranth, and allow horseradish to be planted the following spring.

Classical collective action theories assume that successful political movements must have an organization and the ability to mobilize supporters in support of a common goal. Yet the unprecedented achievements of networked political movements have led scholars to reconsider these assumptions. South Korea’s Nosamo and the Tea Party Movement are unique among networked political movements in that they were aimed at electing specific political candidates. The ability of these two movements successfully to bypass party orthodoxy without a traditional organizational apparatus has bolstered optimism about participatory democracy. However, while both of these movements began as free-flowing horizontal networks, each developed a hierarchical organizational structure. We examine how the development of an organizational structure affected each group’s dominant frame, comparing structures and outcomes in the two cases. In particular, we find out whether there are differences in each group’s ability to affect a unified presence by examining group documents and news coverage. Our results suggest that a cohesive collective action frame is possible without formal organizations, though there may be other requirements that might obtain only under certain circumstances, somewhat weakening prospects for participatory democracy.

Radiative climate feedbacks in the Arctic have been extensively studied, but their spatial and seasonal variations have not been thoroughly examined. Using ERA5 reanalysis data, we examine seasonal variations in Arctic climate feedbacks and their relationship to sea‐ice loss based on changes from 1950–1979 to 1990–2019. The spring and summer seasons experienced large sea‐ice loss, strong surface albedo feedback, and large oceanic heat uptake. Arctic clouds exerted small net cooling in May‐June‐July but moderate warming during the cold season, especially over areas with large sea‐ice loss where cloud liquid and ice water content increased. Arctic water vapor feedback peaked in summer but was weak and uncorrelated with sea‐ice loss. Arctic positive lapse rate feedback (LRF) was strongest in winter over areas with large sea‐ice loss and weak inversion but uncorrelated with atmospheric stability, suggesting that oceanic heating from sea‐ice loss led to enhanced surface warming and the positive LRF. The seasonal and spatial patterns of climate feedbacks—processes that enhance or dampen changes in Earth's surface temperature—have not been thoroughly studied in the Arctic. We examine these variations based on changes between 1950–1979 and 1990–2019 using atmospheric reanalysis data. Large amounts of reflective sea ice melted in spring and summer, allowing the ocean to absorb more sunlight. Clouds slightly cooled the Arctic in May‐June‐July and warmed the Arctic in autumn and winter. The warming effect of increased water vapor was strongest in summer but was weak and not related to sea‐ice loss. Autumn and winter Arctic warming is largest over the areas with sea‐ice loss and heating from exposed ocean surfaces, decreasing the infrared radiative cooling efficiency of the atmosphere. The results suggest a central role of sea‐ice loss in producing large Arctic warming. Arctic positive lapse rate feedback strengthens in winter over areas with large sea‐ice loss, oceanic heating, and surface warmingArctic water vapor feedback peaks in summer but is weak and unrelated to sea‐ice lossWinter Arctic positive cloud feedback strengthens over areas with large sea‐ice loss and increased cloud liquid and ice water content Arctic positive lapse rate feedback strengthens in winter over areas with large sea‐ice loss, oceanic heating, and surface warming Arctic water vapor feedback peaks in summer but is weak and unrelated to sea‐ice loss Winter Arctic positive cloud feedback strengthens over areas with large sea‐ice loss and increased cloud liquid and ice water content

Characterizing black carbon (BC) concentrations in the seasonal snowpack is of interest because BC deposition on snow can reduce albedo and accelerate melt. In Washington State, USA snowmelt from the seasonal snowpack provides an important source of water resources, but minimal work has been done characterizing BC concentrations in snow in this region. BC concentrations in snow were monitored over two winters (2012 and 2013) at Tronsen Meadow, located near Blewett Pass in the eastern Cascade Mountains in Central Washington, to characterize spatial and temporal variations in BC concentrations, and the processes affecting BC concentrations in the snowpack. BC concentrations were measured using a Single Particle Soot Photometer. Snowpit BC concentrations at spatial scales ranging from centimeter to 100 m scales were fairly homogenous during the accumulation season, with greater spatial variability during the melt season due to variable melt patterns. BC concentrations in snow increased in late winter‐spring due to an increase in atmospheric BC concentrations and trapping of BC on the snow surface during melt. However, during a period of intense melt in 2013 BC concentrations decreased, likely caused by meltwater scavenging. In summer 2012 the Table Mountain forest fire burned adjacent to the study site, and BC concentrations in the snowpack in 2013 were far higher than in previous years, with charred trees postfire the likely source of the elevated BC. Spatial variability of snow BC concentrations was constrained on the sub‐100 m scaleBC in the snowpack increases during spring from higher atmospheric BC and meltCharred tree postwildfire results in higher BC concentrations in the snowpack

An interview with composer Michael Finnissy is presented. He shares his reasons for pursuing a career in composition. He believes that there is a certain type of interface between composition and improvisation. He thinks that there is a connection between music and myth because music opens up a lot of channels that ordinary reality does not usually access.

Genomic studies in acute myeloid leukemia (AML) have generated a near complete catalogue of genes mutated at varying frequencies both across patients and in individual leukemias. The high variability of mutation burden within a given leukemia is suggestive of a stepwise evolutionary process composed of early, clonal, mutations and subsequent subclonal events. The receptor tyrosine kinase, FLT3, is the most commonly mutated gene in AML, with mutations frequently manifesting as internal tandem duplications (ITDs) in the juxtamembrane domain leading to constitutive kinase activation. Although FLT3is commonly a subclonal mutational event, FLT3 ITDmutations portend a poor prognosis particularly when combined with DNMT3Aand NPM1, earlier mutations that drive clonal expansion. Notwithstanding its role as a subclonal driver, previous preclinical FLT3models have utilized retroviral overexpression or germline mutant expression at the endogenous locus precluding accurate temporal modeling of disease. These efforts have prohibited evaluation of FLT3mutational acquisition in the context observed in AML patients.

The objectives of the case are to provide an overview of the B2B segment of the e-business industry for students to understand the intricacies of how it functions, an in-depth example of how an industry can be analyzed, and an example of how to identify keys to success for a company, GE Global Exchange Services (GXS). Other subject matter objectives are to provide an example of how a company can identify opportunities and threats in its industry and how to analyze competitive market situations, develop alternative strategies, evaluate the consequences of decision models, and make winning corporate decisions.

Sea‐ice loss and radiative feedbacks have been proposed to explain Arctic amplification (AA)—the enhanced Arctic warming under increased greenhouse gases, but their relationship is unclear. By analyzing coupled CESM1 simulations with 1%/year CO2increases, we show that without large sea‐ice loss and AA, the lapse rate, Planck, and surface albedo feedbacks are greatly reduced, while the positive water vapor feedback changes little. The positive Arctic lapse rate feedback, which results from enhanced surface warming rather than the high stability of Arctic air, and changes in atmospheric energy transport across the Arctic Circle are a result, not a cause, of AA; while the water vapor feedback also plays a minor role. Instead, AA results from enhanced winter oceanic heating associated with sea‐ice loss that is aided by a positive surface albedo feedback in summer and positive cloud feedback in winter. Increased atmospheric greenhouse gases cause large warming in the Arctic. The loss of sea‐ice cover and positive climate feedbacks is proposed to explain the enhanced Arctic warming, but their relationship is unknown. We analyze two climate model simulations with 1%/year increases in atmospheric CO2, one with dynamic sea ice and another with fixed sea ice, to quantify the impact of sea‐ice loss on Arctic feedback processes. We find that without large sea‐ice loss, Arctic lapse rate, Planck, and surface albedo feedbacks are reduced along with smaller Arctic warming. Melting sea ice minimally impacts the water vapor feedback but enhances the cooling effects of clouds in summer. Further, sea‐ice loss increases surface absorption of solar energy in summer and the release of heat from the ocean to the atmosphere in winter, leading to enhanced Arctic warming in winter; while the contributions from the other feedbacks are likely small. Arctic lapse rate, Planck, and surface albedo feedbacks are greatly reduced without large sea‐ice loss and surface warmingArctic positive lapse rate feedback likely results from enhanced surface warming caused by oceanic heatingWinter oceanic heat release and summer albedo feedback are the main causes of Arctic amplification Arctic lapse rate, Planck, and surface albedo feedbacks are greatly reduced without large sea‐ice loss and surface warming Arctic positive lapse rate feedback likely results from enhanced surface warming caused by oceanic heating Winter oceanic heat release and summer albedo feedback are the main causes of Arctic amplification

Contemporary collective action theories put large horizontal digitally connected networks at the center of mass political action. They posit that information sharing among ordinary social media users makes possible new forms of rapid mass political action. However, recent research has shown that influential individuals can play a number of key roles in facilitating networked political action in seemingly leaderless movements. Still, the role of influential individuals in stimulating protest information sharing on social media is an important aspect of networked collective action that remains understudied. This study seeks to address this. Specifically, it investigates the following question: does exposure to appeals to engage in protest increase individuals’ motivation to share protest information? Drawing on evidence from an original survey experiment, this study shows that digital appeals to engage in collective action posted by influential individuals do elicit an increase in motivation to share the appeal. However, this result obtains only for Korean respondents, whereas influential appeals appear to have no effect on Japanese respondents. I argue that this difference is in part a function of different citizenship norms in the two countries, and the corresponding effects on social network dynamics. Preliminary analysis supports this interpretation, but further investigation is warranted.

An interview with Jason Eckardt, a percussionist, composer and co-founder and executive director of Ensemble 21. When asked what made him decide to pursue a musical career, he responds that as a child he was obsessed with music and became serious about playing music after hearing Jimmy Page's guitar solo on Led Zeppelin's "Heartbreaker." He mentions his attraction to music that feature virtuosity. He claims that he wants to be able to push beyond the technical boundaries of music.