Insiders\u27 perspectives on project based learning: A comparison of US and Israeli approaches

High school students and teachers in two countries (US and Israel) were interviewed to ascertain their perspectives about their Project Based Learning (PBL) experiences. Perspectives were evaluated to determine to what degree PBL approaches were based on the eight essential elements of PBL and whether PBL courses contributed effectively to workplace preparedness. Differences between teachers and students and between countries were identified. Results revealed that PBL programs incorporating the eight essential elements are more effective in preparing students to enter today’s work environment. Students perceive stronger benefits from their PBL experiences than teachers perceive. Additionally, the perspectives of Israeli teachers and students were more similar to each other than the perspectives of US teachers and students

Lower Cook Inlet Petroleum Development Scenarios: Economic and Demographic Analysis

The State of Alask

Population Bottlenecks as a Potential Major Shaping Force of Human Genome Architecture

The modern synthetic view of human evolution proposes that the fixation of novel mutations is driven by the balance among selective advantage, selective disadvantage, and genetic drift. When considering the global architecture of the human genome, the same model can be applied to understanding the rapid acquisition and proliferation of exogenous DNA. To explore the evolutionary forces that might have morphed human genome architecture, we investigated the origin, composition, and functional potential of numts (nuclear mitochondrial pseudogenes), partial copies of the mitochondrial genome found abundantly in chromosomal DNA. Our data indicate that these elements are unlikely to be advantageous, since they possess no gross positional, transcriptional, or translational features that might indicate beneficial functionality subsequent to integration. Using sequence analysis and fossil dating, we also show a probable burst of integration of numts in the primate lineage that centers on the prosimian–anthropoid split, mimics closely the temporal distribution of Alu and processed pseudogene acquisition, and coincides with the major climatic change at the Paleocene–Eocene boundary. We therefore propose a model according to which the gross architecture and repeat distribution of the human genome can be largely accounted for by a population bottleneck early in the anthropoid lineage and subsequent effectively neutral fixation of repetitive DNA, rather than positive selection or unusual insertion pressures

Navigating Hurdles:A Review of the Obstacles Facing the Development of the Pandemic Treaty

INTRODUCTION: The emergence of the COVID-19 pandemic has served as a call for enhanced global cooperation and a more robust pandemic preparedness and response framework. As a result of this pressing demand, dialogues were initiated to establish a pandemic treaty designed to foster a synchronized global strategy for addressing forthcoming health emergencies. In this review, we discussed the main obstacles to this treaty.RESULTS: Among several challenges facing the pandemic treaty, we highlighted (1) global cooperation and political will, (2) equity in access to resources and treatments, (3) sustainable financing, (4) compliance and enforcement mechanisms, (5) sovereignty concerns, and (6) data sharing and transparency.CONCLUSION: Navigating the hurdles facing the development of the pandemic treaty requires concerted efforts, diplomatic finesse, and a shared commitment to global solidarity. Addressing challenges in global cooperation, equitable access, transparency, compliance, financing, and sovereignty is essential for forging a comprehensive and effective framework for pandemic preparedness and response on the global stage.</p

Whole-genome approach to assessing human cytomegalovirus dynamics in transplant patients undergoing antiviral therapy

Human cytomegalovirus (HCMV) is the most frequent cause of opportunistic viral infection following transplantation. Viral factors of potential clinical importance include the selection of mutants resistant to antiviral drugs and the occurrence of infections involving multiple HCMV strains. These factors are typically addressed by analyzing relevant HCMV genes by PCR and Sanger sequencing, which involves independent assays of limited sensitivity. To assess the dynamics of viral populations with high sensitivity, we applied high-throughput sequencing coupled with HCMV-adapted target enrichment to samples collected longitudinally from 11 transplant recipients (solid organ, n=9, and allogeneic hematopoietic stem cell, n=2). Only the latter presented multiple-strain infections. Four cases presented resistance mutations (n=6), two (A594V and L595S) at high (100%) and four (V715M, 32 V781I, A809V and T838A) at low (&lt;25%) frequency. One allogeneic hematopoietic stem cell transplant recipient presented up to four resistance mutations, each at low frequency. The use of high throughput sequencing to monitor mutations and strain composition in people at risk of HCMV disease is of potential value in helping clinicians implement the most appropriate therapy

Validation of the SCID-hu Thy/Liv mouse model with four classes of licensed antiretrovirals.

BackgroundThe SCID-hu Thy/Liv mouse model of HIV-1 infection is a useful platform for the preclinical evaluation of antiviral efficacy in vivo. We performed this study to validate the model with representatives of all four classes of licensed antiretrovirals.Methodology/principal findingsEndpoint analyses for quantification of Thy/Liv implant viral load included ELISA for cell-associated p24, branched DNA assay for HIV-1 RNA, and detection of infected thymocytes by intracellular staining for Gag-p24. Antiviral protection from HIV-1-mediated thymocyte depletion was assessed by multicolor flow cytometric analysis of thymocyte subpopulations based on surface expression of CD3, CD4, and CD8. These mice can be productively infected with molecular clones of HIV-1 (e.g., the X4 clone NL4-3) as well as with primary R5 and R5X4 isolates. To determine whether results in this model are concordant with those found in humans, we performed direct comparisons of two drugs in the same class, each of which has known potency and dosing levels in humans. Here we show that second-generation antiretrovirals were, as expected, more potent than their first-generation predecessors: emtricitabine was more potent than lamivudine, efavirenz was more potent than nevirapine, and atazanavir was more potent than indinavir. After interspecies pharmacodynamic scaling, the dose ranges found to inhibit viral replication in the SCID-hu Thy/Liv mouse were similar to those used in humans. Moreover, HIV-1 replication in these mice was genetically stable; treatment of the mice with lamivudine did not result in the M184V substitution in reverse transcriptase, and the multidrug-resistant NY index case HIV-1 retained its drug-resistance substitutions.ConclusionGiven the fidelity of such comparisons, we conclude that this highly reproducible mouse model is likely to predict clinical antiviral efficacy in humans

Environmental signals rather than layered ontogeny imprint the function of type 2 conventional dendritic cells in young and adult mice

Conventional dendritic cells (cDC) are key activators of naive T cells, and can be targeted in adults to induce adaptive immunity, but in early life are considered under-developed or functionally immature. Here we show that, in early life, when the immune system develops, cDC2 exhibit a dual hematopoietic origin and, like other myeloid and lymphoid cells, develop in waves. Developmentally distinct cDC2 in early life, despite being distinguishable by fate mapping, are transcriptionally and functionally similar. cDC2 in early and adult life, however, are exposed to distinct cytokine environments that shape their transcriptional profile and alter their ability to sense pathogens, secrete cytokines and polarize T cells. We further show that cDC2 in early life, despite being distinct from cDC2 in adult life, are functionally competent and can induce T cell responses. Our results thus highlight the potential of harnessing cDC2 for boosting immunity in early life.</p

Protocol for 'Seal or Varnish' (SoV) trial: A randomised controlled trial to measure the relative cost and effectiveness of pit and fissure sealants and fluoride varnish in preventing dental decay

Background Dental caries remains a significant public health problem, prevalence being linked to social and economic deprivation. Occlusal surfaces of first permanent molars are the most susceptible site in the developing permanent dentition. Cochrane reviews have shown pit and fissure sealants (PFS) and fluoride varnish (FV) to be effective over no intervention in preventing caries. However, the comparative cost and effectiveness of these treatments is uncertain. The primary aim of the trial described in this protocol is to compare the clinical effectiveness of PFS and FV in preventing dental caries in first permanent molars in 6-7 year-olds. Secondary aims include: establishing the costs and the relative cost-effectiveness of PFS and FV delivered in a community/school setting; examining the impact of PFS and FV on children and their parents/carers in terms of quality of life/treatment acceptability measures; and examining the implementation of treatment in a community setting. Methods/design The trial design comprises a randomised, assessor-blinded, two-arm, parallel group trial in 6–7 year old schoolchildren. Clinical procedures and assessments will be performed at 66 primary schools, in deprived areas in South Wales. Treatments will be delivered via a mobile dental clinic. In total, 920 children will be recruited (460 per trial arm). At baseline and annually for 36 months dental caries will be recorded using the International Caries Detection and Assessment System (ICDAS) by trained and calibrated dentists. PFS and FV will be applied by trained dental hygienists. The FV will be applied at baseline, 6, 12, 18, 24 and 30 months. The PFS will be applied at baseline and re-examined at 6, 12, 18, 24, and 30 months, and will be re-applied if the existing sealant has become detached/is insufficient. The economic analysis will estimate the costs of providing the PFS versus FV. The process evaluation will assess implementation and acceptability through acceptability scales, a schools questionnaire and interviews with children, parents, dentists, dental nurses and school staff. The primary outcome measure will be the proportion of children developing new caries on any one of up to four treated first permanent molars. Discussion The objectives of this study have been identified by the National Institute for Health Research as one of importance to the National Health Service in the UK. The results of this trial will provide guidance on which of these technologies should be adopted for the prevention of dental decay in the most susceptible tooth-surface in the most at risk children

Phospholipases A1

Phospholipase A1 (PLA1) is an enzyme that hydrolyzes phospholipids and produces 2-acyl-lysophospholipids and fatty acids. This lipolytic activity is conserved in a wide range of organisms but is carried out by a diverse set of PLA1 enzymes. Where their function is known, PLA1s have been shown to act as digestive enzymes, possess central roles in membrane maintenance and remodeling, or regulate important cellular mechanisms by the production of various lysophospholipid mediators, such as lysophosphatidylserine and lysophosphatidic acid, which in turn have multiple biological functions

Using an insect mushroom body circuit to encode route memory in complex natural environments

Ants, like many other animals, use visual memory to follow extended routes through complex environments, but it is unknown how their small brains implement this capability. The mushroom body neuropils have been identified as a crucial memory circuit in the insect brain, but their function has mostly been explored for simple olfactory association tasks. We show that a spiking neural model of this circuit originally developed to describe fruitfly (Drosophila melanogaster) olfactory association, can also account for the ability of desert ants (Cataglyphis velox) to rapidly learn visual routes through complex natural environments. We further demonstrate that abstracting the key computational principles of this circuit, which include one-shot learning of sparse codes, enables the theoretical storage capacity of the ant mushroom body to be estimated at hundreds of independent images