High-Affinity Quasi-Specific Sites in the Genome: How the DNA-Binding Proteins Cope with Them

AbstractMany prokaryotic transcription factors home in on one or a few target sites in the presence of a huge number of nonspecific sites. Our analysis of λ-repressor in the Escherichia coli genome based on single basepair substitution experiments shows the presence of hundreds of sites having binding energy within 3 Kcal/mole of the OR1 binding energy, and thousands of sites with binding energy above the nonspecific binding energy. The effect of such sites on DNA-based processes has not been fully explored. The presence of such sites dramatically lowers the occupation probability of the specific site far more than if the genome were composed of nonspecific sites only. Our Brownian dynamics studies show that the presence of quasi-specific sites results in very significant kinetic effects as well. In contrast to λ-repressor, the E. coli genome has orders of magnitude lower quasi-specific sites for GalR, an integral transcription factor, thus causing little competition for the specific site. We propose that GalR and perhaps repressors of the same family have evolved binding modes that lead to much smaller numbers of quasi-specific sites to remove the untoward effects of genomic DNA

Exploring Goodness of Fit: Social Cognition Among Students with Gifts and Talents in Ireland and India

Utilizing previous research focusing on the Stigma of Giftedness Paradigm (SGP), this study explains social cognitive beliefs with the help of self-efficacy among students with gifts and talents (SWGT) in Ireland and India. The study considers the concept of person-environment fit with respect to how the SWGT feel they are being seen by others and how they react to their environment, where their self-efficacy plays a role. Irish and Indian students (N = 430) were matched by age (15-17) and gender. Data were collected using the Social Cognitive Beliefs scale as an indicator of person-environment fit, and the Multidimensional Scales of Perceived Self-Efficacy. Statistically significant differences were found in social cognition among the two groups with SWGT from Ireland (both males and females) scoring higher, suggesting a poorer fit with peers among them. However, the younger (15 and 16 years old) Indian SWGT had lower scores in peer-related social cognition than all Irish SWGT indicating a better fit with peers. Further, a hierarchical linear regression revealed self-regulated learning as a positive contributor and enlisting parental and community support as a negative contributor to explain social cognition beliefs among both Irish and Indian SWGT. Interestingly, while resisting peer pressure was a positive contributor for the Irish SWGT, it was a negative contributor for the Indian SWGT. Variations in results observed among the SWGT of the two countries are discussed with respect to cultural differences. The study not only contributes to an argument for SWGT to learn in environments where they are surrounded by intellectual peers with similar seriousness and abilities, but also draws attention to both fit in the environment and students’ confidence in their abilities by bringing in a cross-cultural perspective

El narcoperiodismo de García Márquez: uma análise dos aspectos da narcoliteratura no livro-reportagem Notícia de um sequestro

Desde os anos 1970, a cobertura da mídia tradicional sobre o narcotráfico caracterizou-se pela superficialidade de suas narrativas cujo processo impossibilita a profundidade de análise. Porém, alguns repórteres foram bem-sucedidos ao aproximar o narcotráfico e o jornalismo literário, rompendo com essa barreira limitante, principalmente, a partir da produção de livros-reportagem. O tema influenciou a literatura do continente (originando termos como narcoliteratura, narconarrativa e narcocultura), bem como o contexto do tráfico de drogas proporcionou a produção editorial de obras de não ficção, a partir dos final dos anos 80, atingindo o ápice nos anos 90 e 2000. Desta forma, este artigo discute o papel do livro-reportagem para a produção cultural da narcoliteratura, a partir de uma análise de seus aspectos dentro da obra jornalística Notícia de um sequestro (1996), de Gabriel García Márquez. O artigo está apoiado nos conceitos de livro-reportagem, de Edvaldo Pereira Lima e nas discussões sobre narcocultura, de Omar Rincón e de Diana Palaversich

Artificial intelligence for diagnosis and Gleason grading of prostate cancer: The PANDA challenge

Through a community-driven competition, the PANDA challenge provides a curated diverse dataset and a catalog of models for prostate cancer pathology, and represents a blueprint for evaluating AI algorithms in digital pathology. Artificial intelligence (AI) has shown promise for diagnosing prostate cancer in biopsies. However, results have been limited to individual studies, lacking validation in multinational settings. Competitions have been shown to be accelerators for medical imaging innovations, but their impact is hindered by lack of reproducibility and independent validation. With this in mind, we organized the PANDA challenge-the largest histopathology competition to date, joined by 1,290 developers-to catalyze development of reproducible AI algorithms for Gleason grading using 10,616 digitized prostate biopsies. We validated that a diverse set of submitted algorithms reached pathologist-level performance on independent cross-continental cohorts, fully blinded to the algorithm developers. On United States and European external validation sets, the algorithms achieved agreements of 0.862 (quadratically weighted kappa, 95% confidence interval (CI), 0.840-0.884) and 0.868 (95% CI, 0.835-0.900) with expert uropathologists. Successful generalization across different patient populations, laboratories and reference standards, achieved by a variety of algorithmic approaches, warrants evaluating AI-based Gleason grading in prospective clinical trials.KWF Kankerbestrijding ; Netherlands Organization for Scientific Research (NWO) ; Swedish Research Council European Commission ; Swedish Cancer Society ; Swedish eScience Research Center ; Ake Wiberg Foundation ; Prostatacancerforbundet ; Academy of Finland ; Cancer Foundation Finland ; Google Incorporated ; MICCAI board challenge working group ; Verily Life Sciences ; EIT Health ; Karolinska Institutet ; MICCAI 2020 satellite event team ; ERAPerMe

Reporting trends, practices, and resource utilization in neuroendocrine tumors of the prostate gland: a survey among thirty-nine genitourinary pathologists

Background: Neuroendocrine differentiation in the prostate gland ranges from clinically insignificant neuroendocrine differentiation detected with markers in an otherwise conventional prostatic adenocarcinoma to a lethal high-grade small/large cell neuroendocrine carcinoma. The concept of neuroendocrine differentiation in prostatic adenocarcinoma has gained considerable importance due to its prognostic and therapeutic ramifications and pathologists play a pivotal role in its recognition. However, its awareness, reporting, and resource utilization practice patterns among pathologists are largely unknown. Methods: Representative examples of different spectrums of neuroendocrine differentiation along with a detailed questionnaire were shared among 39 urologic pathologists using the survey monkey software. Participants were specifically questioned about the use and awareness of the 2016 WHO classification of neuroendocrine tumors of the prostate, understanding of the clinical significance of each entity, and use of different immunohistochemical (IHC) markers. De-identified respondent data were analyzed. Results: A vast majority (90%) of the participants utilize IHC markers to confirm the diagnosis of small cell neuroendocrine carcinoma. A majority (87%) of the respondents were in agreement regarding the utilization of type of IHC markers for small cell neuroendocrine carcinoma for which 85% of the pathologists agreed that determination of the site of origin of a high-grade neuroendocrine carcinoma is not critical, as these are treated similarly. In the setting of mixed carcinomas, 62% of respondents indicated that they provide quantification and grading of the acinar component. There were varied responses regarding the prognostic implication of focal neuroendocrine cells in an otherwise conventional acinar adenocarcinoma and for Paneth cell-like differentiation. The classification of large cell neuroendocrine carcinoma was highly varied, with only 38% agreement in the illustrated case. Finally, despite the recommendation not to perform neuroendocrine markers in the absence of morphologic evidence of neuroendocrine differentiation, 62% would routinely utilize IHC in the work-up of a Gleason score 5 + 5 = 10 acinar adenocarcinoma and its differentiation from high-grade neuroendocrine carcinoma. Conclusion: There is a disparity in the practice utilization patterns among the urologic pathologists with regard to diagnosing high-grade neuroendocrine carcinoma and in understanding the clinical significance of focal neuroendocrine cells in an otherwise conventional acinar adenocarcinoma and Paneth cell-like neuroendocrine differentiation. There seems to have a trend towards overutilization of IHC to determine neuroendocrine differentiation in the absence of neuroendocrine features on morphology. The survey results suggest a need for further refinement and development of standardized guidelines for the classification and reporting of neuroendocrine differentiation in the prostate gland

Gifted education in India

In the backdrop of India’s growing population of 1.21 billion people with diverse, multicultural and multilingual backgrounds, gifted education is yet to be part of a formal educational policy in the country. Research on giftedness in India spans across 50 years, but lacks systematic and empirical grounding. The term “gifted” in the Indian context has not been used till very recently and most Indian studies have focused on creativity. Talented children in India are recognized at both homes and schools but formal identification and nurture of giftedness is sporadic and mostly dependent whether the child has been selected for gifted programs which are far and few. The lack of adequate information and database about programs, policies, practices, and outcomes in gifted education in India make it impossible for accurate review. Through the article, the author attempts to provide an insight about India’s views on gifted education and giftedness, the challenges it faces in introducing gifted education as a part of its national educational policy. A commentary on the contributions made by several individuals and institutions to gifted education in India despite a policy and funding vacuum has also been presented

Study of effectiveness of online classes among undergraduate medical students during COVID-19 pandemic

Introduction: Due to the pandemic COVID-19 the medical education has shifted to the virtual mode in almost all the countries. Online learning is being practiced for quite some time and it has proved to be useful but its effectiveness should be anticipated for countries like India. Methods: An online survey was conducted among undergraduate medical and allied health students with the help of a structured self-administered questionnaire consisting of demographic information, modalities of online classes they are attending and their impression regarding the online classes. Results: Maximum students had access to devices and internet but some of the students responded that they have no internet facility at home. More than half of the students have responded that they are facing some sort of visual problem after online classes have commenced. Many students responded that the internet connectivity issue is a hindrance to online learning. Greater number of the students strongly disagree that online class should be continued even after the pandemic is over. Conclusion: There are lots of obstacles in virtual learning in resource-limited countries like ours. The efficiency of e-learning should be assessed among the students and the flaws of virtual learning are to be dealt by concerned authorities

Pd(0), Pt(II) catalyzed carbon-carbon bond formation across tetragonal tin (II) oxide: Synthesis of ferrocenes with ene-appendage

2416-2421Alkenylferrocenes, FcCHCHCHCH2 have been synthesized from formylferrocene and allyl halides using β-SnO and Pd(0) or Pt(II) as co-catalyst in organic aqueous medium. Monoallylated products have been isolated by similar reaction with 1,1ʹ-bis-formylferrocene. These serve as potential precursors for multinuclear ferrocenophanes with extended conjugated ene-spacer