Class-switch DNA recombination (CSR) of the immunoglobulin heavy chain (IGH) locus is central to the maturation of the antibody response and crucially requires the cytidine deaminase AID. CSR ...involves changes in the chromatin state and the transcriptional activation of the IGH locus at the upstream and downstream switch (S) regions that are to undergo S-S DNA recombination. In addition, CSR involves the induction of AID expression and the targeting of CSR factors to S regions by 14-3-3 adaptors, and it is facilitated by the transcription machinery and by histone modifications. In this Review, we focus on recent advances regarding the induction and targeting of CSR and outline an integrated model of the assembly of macromolecular complexes that transduce crucial epigenetic information to enzymatic effectors of the CSR machinery.
In 1984, the oil, chemical and atomic workers began a 5-year campaign to win back the jobs of its members locked out by the BASF Corp. in Geismar, Louisiana. The multiscale campaign involved ...coalitions with local environmentalists as well as international solidarity from environmental and religious organizations. The local coalition which helped break the lockout was maintained and expanded in the 1990s. This alliance is one of numerous labor-community coalitions to emerge increasingly over the past 20 years.""Labor-Environmental Coalitions: Lessons from a Louisiana Petrochemical Region"" traces the development of the Louisiana Labor-Neighbor Project from 1985 to the present, within the context of a long history of divisions between labor and community in the U.S. The Project continued after the lockout, thriving during 1990s, expanding from one community to four counties to include 20 local member organizations, and broadening its agenda from the original jobs crisis and pollution problems to address a wide range of worker, environmental health, and economic justice issues."" Labor-Environmental Coalitions"" explores the dynamics of the Louisiana coalition to offer lessons for other coalition efforts. The book seeks to understand coalitions as a necessary strategy to counteract the dominant forces of capitalist development. The author contends that the Labor-Neighbor Project, like labor-community coalitions generally, created a unique blend of politics shaped by the geographic nature industry's politics; by the relative openness of government; and by the class experience of labor and community members.The Louisiana Project demonstrates that for labor-community coalitions to thrive they must broaden their agenda, strengthen their leadership and coalition-building skills, and develop access to multiscale resources. The author argues that for labor-community coalitions to have longer term political impact, they should adopt an explicitly progressive approach by building a broader class and cultural leadership, and by demanding state and corporate accountability on economic, public health, and environmental justice issues.
Background
Despite the many advantages of flipped learning, it is challenging for educators to ensure that students complete the pre‐class learning assignments before the in‐class session.
Objectives
...Using a learning analytics approach, this study analysed students' pre‐class video‐watching behaviour in flipped learning with a focus on learners' resource management strategies, procrastination, and repeated video‐watching.
Methods
For the empirical study, three types of data (i.e., log data, survey and exam) were obtained from 70 undergraduate students who were enrolled in pre‐service teacher program designed in a flipped classroom including pre‐class videos and in‐class session.
Results and conclusions
The findings showed significant differences between the non‐procrastination group and procrastination group in their video watching time and resource management strategies. Those who watched the pre‐class videos at home/dorm greatly outnumbered those who did not, and they performed better than students who watched the pre‐class videos in other locations.
What are the major takeaways from the study?
This finding highlights the importance of resource management strategies in terms of the time and study environment to promote success in flipped learning courses. However, the number of times students accessed the pre‐class videos or watched the videos before class was not correlated with learning achievement. The reason for re‐watching pre‐class videos is a suggested future direction so instructors can design effective flipped learning courses.
Lay Description
What is already known about this topic?
Flipped learning is a type of blended learning that combines two teaching and learning modes: face‐to‐face learning and online learning. The effectiveness of flipped learning has also been demonstrated in many empirical studies and meta‐analyses.
Despite the many advantages of flipped learning, it is challenging to ensure that students complete the pre‐class materials before class.
Data‐driven decisions based on the learning analytics approach can help instructors revise the in‐class activities more adoptively and individual learners can be more engaged in flipped learning.
What this paper adds?
Using a learning analytics approach, this study analysed students' pre‐class video‐watching behaviour in flipped learning with a focus on learners' resource management strategies, procrastination, and repeated video‐watching.
We also examined the correlations among pre‐class video‐watching behaviour variables and learning achievement.
This study highlights the following: (1) The no‐procrastination group had better resource management strategies than the procrastination group; (2) students who watched pre‐class videos at home outperformed those who watched them in other locations: (3) the number of times students accessed pre‐class videos was not correlated with learning achievement; and (4) whether or not students watched pre‐class videos prior to the in‐class sessions was not correlated with learning achievement.
Implications for practise and/or policy
Although flipped learning gives students considerable autonomy in terms of when and where to watch pre‐class videos at their convenience, it is necessary to help students develop resource management strategies by providing role models, best practises, and statistics in previous flipped learning classes.
Research findings suggest that instructors should provide guidelines and learning strategies on how to review or repeat the pre‐class videos to improve the quality of learning.
To encourage students to repeat the videos, the pre‐class videos should be short and concise.
This paper contributes to the study of social change by considering boundary work as a dimension of cultural change. Drawing on the computer‐assisted qualitative analysis of 73 formal speeches made ...by Donald Trump during the 2016 electoral campaign, we argue that his political rhetoric, which led to his presidential victory, addressed the white working class's concern with their declining position in the national pecking order. He addressed this group's concern by raising their moral status, that is, by (1) emphatically describing them as hard‐working Americans who are victims of globalization; (2) voicing their concerns about ‘people above’ (professionals, the rich, and politicians); (3) drawing strong moral boundaries toward undocumented immigrants, refugees, and Muslims; (4) presenting African Americans and (legal) Hispanic Americans as workers who also deserve jobs; (5) stressing the role of working‐class men as protectors of women and LGBTQ people. This particular case study of the role of boundary work in political rhetoric provides a novel, distinctively sociological approach for capturing dynamics of social change.
•The new classifier jointly optimizes true positive and true negative rates for imbalanced data while simultaneously minimizing weighted risk.•It outperforms the existing random forests method in ...complex settings of rare minority instances, high dimensionality and highly imbalanced data.•Its performance is superior with respect to variable selection for imbalanced data.•The classifier is also highly competitive for multiclass imbalanced data.
Extending previous work on quantile classifiers (q-classifiers) we propose the q*-classifier for the class imbalance problem. The classifier assigns a sample to the minority class if the minority class conditional probability exceeds 0 < q* < 1, where q* equals the unconditional probability of observing a minority class sample. The motivation for q*-classification stems from a density-based approach and leads to the useful property that the q*-classifier maximizes the sum of the true positive and true negative rates. Moreover, because the procedure can be equivalently expressed as a cost-weighted Bayes classifier, it also minimizes weighted risk. Because of this dual optimization, the q*-classifier can achieve near zero risk in imbalance problems, while simultaneously optimizing true positive and true negative rates. We use random forests to apply q*-classification. This new method which we call RFQ is shown to outperform or is competitive with existing techniques with respect to G-mean performance and variable selection. Extensions to the multiclass imbalanced setting are also considered.
We investigated the value of tumor-infiltrating NK (TI-NK) cells and HLA class I tumor expression as biomarkers of response to neoadjuvant anti-HER2 antibody-based treatment in breast cancer.
TI-NK ...cells and HLA-I were determined by IHC in pretreatment tumor biopsies from two cohorts of patients with HER2-positive breast cancer discovery cohort (
= 42) and validation cohort (
= 71). Tumor-infiltrating lymphocytes (TIL) were scored according to international guidelines. Biomarker association with pathologic complete response (pCR) and disease-free survival (DFS) was adjusted for prognostic factors. Gene set variation analysis was used for determining immune cell populations concomitant to NK-cell enrichment in HER2-positive tumors from the Cancer Genome Atlas (
= 190).
TI-NK cells were significantly associated with pCR in the discovery cohort as well as in the validation cohort (
< 0.0001), independently of clinicopathologic factors. A ≥3 TI-NK cells/50x high-power field (HPF) cutoff predicted pCR in the discovery and validation cohort OR, 188 (11-3154); OR, 19.5 (5.3-71.8). Presence of TI-NK cells associated with prolonged DFS in both patient cohorts HR, 0.07 (0.01-0.6);
= 0.01; HR, 0.3 (0.08-1.3);
= 0.1. NK-, activated dendritic- and CD8 T-cell gene expression signatures positively correlated in HER2-positive tumors, supporting the value of NK cells as surrogates of effective antitumor immunity. Stratification of patients by tumor HLA-I expression identified patients with low and high relapse risk independently of pCR.
This study identifies baseline TI-NK cells as an independent biomarker with great predictive value for pCR to anti-HER2 antibody-based treatment and points to the complementary value of tumor HLA-I status for defining patient prognosis independently of pCR.
Worldwide Salmonella enterica infections result in substantial morbidity and mortality and are the major cause of infant bacteremia in Sub-Saharan Africa. Diseases caused by Salmonella are treatable ...with antibiotics, but successful antibiotic treatment has become difficult due to antimicrobial resistance and collateral effects on the microbiome. An effective vaccine together with public health efforts may be a better strategy to control these infections. Protective immunity against Salmonella depends primarily on CD4 T-cell-mediated immune responses; therefore, identifying relevant T-cell antigens is necessary for Salmonella vaccine development. We previously used a dendritic-cell-based immunoproteomics approach in our laboratory to identify T-cell antigens. The testing of these antigens as vaccine candidates against Chlamydia infection in mice yielded positive results. We applied this technology in the present study by infecting murine bone-marrow-derived dendritic cells from C57BL/6 mice with Salmonella enterica strain SL1344, followed by immunoaffinity isolation of MHC class I and II molecules and elution of bound peptides. The sequences of the peptides were identified using tandem mass spectrometry. We identified 87 MHC class-II- and 23 MHC class-I-binding Salmonella-derived peptides. Four of the 12 highest scoring class-II-binding Salmonella peptides stimulated IFN-γ production by CD4+ T cells from the spleens of mice with persistent Salmonella infection. We conclude that antigens identified by MHC immunoproteomics will be useful for Salmonella immunobiology studies and are potential Salmonella vaccine candidates. Data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the data set identifier PXD004451.
This study explored students' perceptions of a flipped classroom for an introductory programming class. Students were required to watch video lectures and read lecture notes in advance (pre-class ...self-study) to prepare themselves for the in-class lectures and tutorials. A mix-methods approach was employed: quantitative survey (n=204) and qualitative interview (n=7) were administered simultaneously. The results suggested that students are not fully ready for a flipped classroom. Most of the students still prefer face-to-face in-class lectures and tutorials. The in-class activities have a positive impact on students' test performance, especially the male students. Peer learning however induces a negative impact on students' test performance, especially among the female students. Pre-class self-study has no impact on students' test performance, except for those without prior programming experience. Females outperform males even though they lack prior programming experience. Students, regardless of programming background, respond equally to a flipped classroom approach.
When Steven Burd, CEO of the supermarket chain Safeway, cut wages and benefits, starting a five-month strike by 59, 000 unionized workers, he was confident he would win. But where traditional labor ...action failed, a novel approach was more successful. With the aid of the California Public Employees' Retirement System, a $300 billion pension fund, workers led a shareholder revolt that unseated three of Burd's boardroom allies.In The Rise of the Working-Class Shareholder: Labor's Last Best Weapon, David Webber uses cases such as Safeway's to shine a light on labor's most potent remaining weapon: its multitrillion-dollar pension funds. Outmaneuvered at the bargaining table and under constant assault in Washington, state houses, and the courts, worker organizations are beginning to exercise muscle through markets. Shareholder activism has been used to divest from anti-labor companies, gun makers, and tobacco; diversify corporate boards; support Occupy Wall Street; force global warming onto the corporate agenda; create jobs; and challenge outlandish CEO pay. Webber argues that workers have found in labor's capital a potent strategy against their exploiters. He explains the tactic's surmountable difficulties even as he cautions that corporate interests are already working to deny labor's access to this powerful and underused tool. The Rise of the Working-Class Shareholder is a rare good-news story for American workers, an opportunity hiding in plain sight. Combining legal rigor with inspiring narratives of labor victory, Webber shows how workers can wield their own capital to reclaim their strength.
Prompted by new data and a renewed concern about equality of opportunity, the study of intergenerational mobility has flourished in Latin America in the past decade. Although analysis is still ...restricted to a handful of countries, one conclusion appears clear: Intergenerational income mobility is weaker in Latin America than in industrial countries and is characterized by "persistence at the top," a pattern consistent with the high levels of economic concentration in the region. However, social class mobility in Latin America does not differ from that in the industrialized world. This essay reviews two generations of mobility research since the 1960s, takes stock of current findings on economic and class mobility in Latin America, examines the linkages between mobility and macro-level factors, and engages a new literature on equality of opportunity. I suggest that the comparative understanding of mobility in Latin America can inform and inspire research in the industrialized world.
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