Bringing Together Mentoring, Technology, and Whole-School Reform: A First Look at the iMentor College Ready Program

The iMentor College Ready Program is a unique model that combines elements of school-based mentoring, whole school reform, and technology in an effort to help students develop the knowledge, behaviors, and skills needed to reach and succeed in college. It is an intensive, four-year intervention offered in schools that serve low-income students. Students are paired with volunteer, college-educated mentors and enrolled in an iMentor class led by a school-based iMentor employee.The program has four central elements: A whole school model, which aims to match all incoming 9thgraders with a mentor, and keep them engaged for their full high school careers;A college-readiness curriculum developed by iMentor, taught by iMentor staff in weekly classes, and reinforced during monthly events for mentees and mentors;A "blended" approach to developing relationships between students and their mentor. Students communicate with their mentor primarily through email, but also meet in person at the iMentor events; andA pair support strategy based on a case-management model for tracking mentee-mentor relationship development.The Research Alliance for New York City Schools is conducting an in-depth evaluation of the iMentor College Ready Program in eight New York City high schools. With support from the Social Innovation Fund, the Research Alliance is examining iMentor's roll-out and implementation in these schools, as well as its impact on a range of outcomes related to students' preparation for college. This report is the first in a series from our evaluation. It focuses on iMentor's first year of implementation, which targeted 9th graders in all eight schools. The report provides a detailed description of the four key components of the iMentor College Ready Program and assesses the implementation of these program elements against specific benchmarks established by iMentor. The report also presents a first look at iMentor's effects on 9th graders' outcomes, including their perception of adult support, their aspirations for the future, a set of important college-related "non-cognitive" skills, and several markers of academic achievement

Prevalence and patterns of higher-order drug interactions in Escherichia coli.

Interactions and emergent processes are essential for research on complex systems involving many components. Most studies focus solely on pairwise interactions and ignore higher-order interactions among three or more components. To gain deeper insights into higher-order interactions and complex environments, we study antibiotic combinations applied to pathogenic Escherichia coli and obtain unprecedented amounts of detailed data (251 two-drug combinations, 1512 three-drug combinations, 5670 four-drug combinations, and 13608 five-drug combinations). Directly opposite to previous assumptions and reports, we find higher-order interactions increase in frequency with the number of drugs in the bacteria's environment. Specifically, as more drugs are added, we observe an elevated frequency of net synergy (effect greater than expected based on independent individual effects) and also increased instances of emergent antagonism (effect less than expected based on lower-order interaction effects). These findings have implications for the potential efficacy of drug combinations and are crucial for better navigating problems associated with the combinatorial complexity of multi-component systems

Semi-analytic model predictions of the galaxy population in protoclusters

We investigate the galaxy population in simulated protocluster regions using a semi-analytic model of galaxy formation, coupled to merger-trees extracted from N-body simulations. We select the most massive clusters at redshift z = 0 from our set of simulations, and follow their main progenitors back in time. The analysis shows that protocluster regions are dominated by central galaxies and their number decreases with time as many become satellites, clustering around the central object. In agreement with observations, we find an increasing velocity dispersion with cosmic time, the increase being faster for satellites. The analysis shows that protoclusters are very extended regions, 7320 Mpc at z 73 1. The fraction of galaxies in protocluster regions that are not progenitor of cluster galaxies varies with redshift, stellar mass and area considered. It is about 20-30 per cent for galaxies with stellar mass \u2dc109 M 99, while negligible for the most massive galaxies considered. Nevertheless, these objects have properties similar to those of progenitors. We investigate the building-up of the passive sequence in clusters, and find that their progenitors are on average always active at any redshift of interest of protoclusters. The main mechanism which quenches their star formation is the removal of the hot gas reservoir at the time of accretion. The later galaxies are accreted (become satellite), and the more the cold gas available, the longer the time spent as active. Central galaxies are active over all redshift range considered, although a non-negligible fraction of them become passive at redshift z < 1, due to strong feedback from active galactic nuclei

Hierarchical accumulation of RyR post-translational modifications drives disease progression in dystrophic cardiomyopathy

Aims Duchenne muscular dystrophy (DMD) is a muscle disease with serious cardiac complications. Changes in Ca2+ homeostasis and oxidative stress were recently associated with cardiac deterioration, but the cellular pathophysiological mechanisms remain elusive. We investigated whether the activity of ryanodine receptor (RyR) Ca2+ release channels is affected, whether changes in function are cause or consequence and which post-translational modifications drive disease progression. Methods and results Electrophysiological, imaging, and biochemical techniques were used to study RyRs in cardiomyocytes from mdx mice, an animal model of DMD. Young mdx mice show no changes in cardiac performance, but do so after ∼8 months. Nevertheless, myocytes from mdx pups exhibited exaggerated Ca2+ responses to mechanical stress and ‘hypersensitive' excitation-contraction coupling, hallmarks of increased RyR Ca2+ sensitivity. Both were normalized by antioxidants, inhibitors of NAD(P)H oxidase and CaMKII, but not by NO synthases and PKA antagonists. Sarcoplasmic reticulum Ca2+ load and leak were unchanged in young mdx mice. However, by the age of 4-5 months and in senescence, leak was increased and load was reduced, indicating disease progression. By this age, all pharmacological interventions listed above normalized Ca2+ signals and corrected changes in ECC, Ca2+ load, and leak. Conclusion Our findings suggest that increased RyR Ca2+ sensitivity precedes and presumably drives the progression of dystrophic cardiomyopathy, with oxidative stress initiating its development. RyR oxidation followed by phosphorylation, first by CaMKII and later by PKA, synergistically contributes to cardiac deterioratio

Complex carbohydrate recognition by proteins: Fundamental insights from bacteriophage cell adhesion systems

SummaryProtein–glycan interactions are ubiquitous in nature. Molecular description of complex formation and the underlying thermodynamics, however, are not well understood due to the lack of model systems. Bacteriophage tailspike proteins (TSP) possess binding sites for bacterial cell surfaces oligosaccharides. In this article we describe the analysis of TSP-oligosaccharide complexes. TSP provide large glycan interaction sites where affinity and specificity are guided by the protein surface solvation and the conformational space sampled by the respective glycan. Furthermore, we describe a computational approach to analyse the conformational space sampled by flexible glycans of bacterial origin, a prerequisite for a thorough understanding of TSP-oligosaccharide interactions

Structure, phosphorylation and U2AF65 binding of the N-terminal domain of splicing factor 1 during 3′-splice site recognition

Recognition of the 3′-splice site is a key step in pre-mRNA splicing and accomplished by a dynamic complex comprising splicing factor 1 (SF1) and the U2 snRNP auxiliary factor 65-kDa subunit (U2AF65). Both proteins mediate protein-protein and protein-RNA interactions for cooperative RNA-binding during spliceosome assembly. Here, we report the solution structure of a novel helix-hairpin domain in the N-terminal region of SF1 (SF1NTD). The nuclear magnetic resonance- and small-angle X-ray scattering-derived structure of a complex of the SF1NTD with the C-terminal U2AF homology motif domain of U2AF65 (U2AF65UHM) reveals that, in addition to the known U2AF65UHM-SF1 interaction, the helix-hairpin domain forms a secondary, hydrophobic interface with U2AF65UHM, which locks the orientation of the two subunits. Mutational analysis shows that the helix hairpin is essential for cooperative formation of the ternary SF1-U2AF65-RNA complex. We further show that tandem serine phosphorylation of a conserved Ser80-Pro81-Ser82-Pro83 motif rigidifies a long unstructured linker in the SF1 helix hairpin. Phosphorylation does not significantly alter the overall conformations of SF1, SF1-U2AF65 or the SF1-U2AF65-RNA complexes, but slightly enhances RNA binding. Our results indicate that the helix-hairpin domain of SF1 is required for cooperative 3′-splice site recognition presumably by stabilizing a unique quaternary arrangement of the SF1-U2AF65-RNA comple

Inductive mechcharger: mechanical phone charging dock using faraday's law

Energy and the environment are the key issues of the world in recent decades Requests for the quest for alternative energy sources has become a response to rising energy sources science and technology one of the top priorities. Over 90% of the global population power produced is based on electromagnetic induction laws from faraday. Thus, Free Energy / Electricity interests are becoming popular. The definition of free energy is a misconception. Nothing like free energy is there. But if we use tools like Solar, Wind, Tidal, and Hydro-Electric to produce it, Geothermal is free of charge only after the initial cost of capital. After the fact, the produced energy is free, that the electricity created by these unorthodox methods of electrical power generation must not be compensated for. Therefore, for some time, the idea of electricity generation with magnets has been around. They are used to generate energy through their magnetic fields. These magnets are mounted in engine and generator cores. The basic theory of power generation lies in the magnetic effect. "When the vehicle rotates in a magnet field, a voltage is generated in the car." [1,2

Early and nonreversible decrease of CD161++ /MAIT cells in HIV infection

HIV infection is associated with immune dysfunction, perturbation of immune-cell subsets and opportunistic infections. CD161++ CD8+ T cells are a tissue-infiltrating population that produce IL17A, IL22, IFN, and TNFα, cytokines important in mucosal immunity. In adults they dominantly express the semi-invariant TCR Vα7.2, the canonical feature of mucosal associated invariant T (MAIT) cells and have been recently implicated in host defense against pathogens. We analyzed the frequency and function of CD161++ /MAIT cells in peripheral blood and tissue from patients with early stage or chronic-stage HIV infection. We show that the CD161++ /MAIT cell population is significantly decreased in early HIV infection and fails to recover despite otherwise successful treatment. We provide evidence that CD161++ /MAIT cells are not preferentially infected but may be depleted through diverse mechanisms including accumulation in tissues and activation-induced cell death. This loss may impact mucosal defense and could be important in susceptibility to specific opportunistic infections in HIV

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts