Ultrafast all-optical wavelength conversion in silicon waveguides using femtosecond pump-probe pulses

Experimental results on ultrafast all-optical wavelength conversion in silicon-on-insulator waveguides are presented. Red and blue shifts of 10nm have been observed in femtosecond pump-probe experiments. Alloptical switching and the importance of waveguide dispersion are discussed

In vitro and in vivo expression of foreign genes by transmissible gastroenteritis coronavirus-derived minigenomes

A helper-dependent expression system based on transmissible gastroenteritis coronavirus (TGEV) has been developed using a minigenome of 3·9 kb (M39). Expression of the reporter gene {beta}-glucuronidase (GUS) (2–8 µg per 106 cells) and the porcine respiratory and reproductive syndrome virus (PRRSV) ORF5 (1–2 µg per 106 cells) has been shown using a TGEV-derived minigenome. GUS expression levels increased about eightfold with the m.o.i. and were maintained for more than eight passages in cell culture. Nevertheless, instability of the GUS and ORF5 subgenomic mRNAs was observed from passages five and four, respectively. About a quarter of the cells in culture expressing the helper virus also produced the reporter gene as determined by studying GUS mRNA production by in situ hybridization or immunodetection to visualize the protein synthesized. Expression of GUS was detected in the lungs, but not in the gut, of swine immunized with the virus vector. Around a quarter of lung cells showing replication of the helper virus were also positive for the reporter gene. Interestingly, strong humoral immune responses to both GUS and PRRSV ORF5 were induced in swine with this virus vector. The large cloning capacity and the tissue specificity of the TGEV-derived minigenomes suggest that these virus vectors are very promising for vaccine development

Failure of a geotextile-reinforced embankment using the material point method (MPM)

In a wide spectrum of geotechnical applications, materials undergo large deformations and/or large displacements. On modeling these problems with a Lagrangian finite element method, the mesh can become too distorted and re-meshing is essential. In the past decades, considerable efforts have been made to adopt what is called meshfree methods to mitigate the problems related to mesh distortion. One of these methods is the Material Point Method (MPM) that represents the continuum field as Lagrangian material points (particles), which can move through the fixed background of an Eulerian mesh. In this paper, the tensile membrane is modeled using the coupled FEM-MPM approach which adopts two-dimensional triangular elements for the membrane discretisation which is free to move through a three-dimensional mesh of non-structured tetrahedral elements. Apart from the membrane, the soil is treated with the classical procedure of MPM. To show the potential of the method and the presented membrane scheme, a failure of an embankment with and without geotextile has been presented in this paper. The analyses of failure mechanism and the embankment stability using undrained conditions were investigated to determine the critical embankment height and the corresponding geotextile forces. For the sake of comparison, Plaxis 2D with large deformation formulation is considered as a reference solution

The Impact of a Flipped Classroom on Student Achievement in Mathematics, Science and Physical Education Classrooms

This study was designed to examine the effects of the flipped classroom model. Our study was conducted in Physical Education, Mathematics, and Science classrooms in the Bismarck Public Schools district. The participants were in both the middle and high school levels within the same school district. Data collection methods included a pre-assessment survey, written assignments, a student behavior checklist, and a post-assessment survey. The results of our study showed that students enjoyed learning with the flipped classroom method, completion rates were higher than previously observed, and students were successful at mastering classroom content. According to our student survey, the main benefits to the flipped classroom, were the ability to view lessons without distractions and to view them multiple times. We will continue to look into the benefits of the flipped classroom through the analysis of standardized test scores and classroom assessments

Human monoclonal antibodies to Plasmodium falciparum circumsporozoite protein for transient passive protection of malaria travelers to endemic areas

Plasmodium falciparum, is a protozoa that causes over 214 million cases of Malaria worldwide and the World Health Organization reported an estimated 438,000 deaths attributed to malaria in 2015. Current prevention strategies have reduced malaria cases but they are either costly, have poor efficacy or resistance has begun to develop. There is a global need for an effective pre-exposure prophylaxis treatment. The leading Malaria vaccine candidate is RTS,S which contains a monovalent Plasmodium falciparum circumsporozoite protein (CSP). The goal of this vaccine is to induce anti-CSP antibodies that would block sporozoite invasion of hepatocytes and thereby hinder parasite development into a blood-stage infection that causes malaria morbidity and mortality. Antibodies isolated from individuals who have received the RTS,S vaccine have been shown to prevent infection of hepatocytes, suggesting that CSP antibodies could be used prophylactically. However, phase III trial results of the vaccine have shown underwhelming efficacy in children. Growing resistance to transient protection strategies for travelers and low efficacy in vaccine trials suggest there is a need for a new treatment strategy. The generation of CSP specific human monoclonal antibodies (mAbs) would be useful as prevention especially for individuals that are temporarily exposed to Malaria in endemic regions such as travelers or military personnel. Isolation and production of therapeutic mAbs traditionally utilizes a handful of techniques including antibody engineering, phage display or hybridoma generation from transgenic mice. We have sorted antigen-specific memory B-cells from the peripheral blood of children naturally infected with malaria to isolate CSP-specific memory B-cells. These cells were individually sorted and PCR was performed to amplify antibody variable regions of the B-cell’s antibody mRNA. Samples that produced heavy and light chain antibody sequence were cloned and transiently expressed. We plan to characterize these mAbs for binding and neutralization of CSP to identify functional therapeutic mAbs

International Network for Capacity Building for the Control of Emerging Viral Vector-Borne Zoonotic Diseases: Arbo-Zoonet

Arboviruses are arthropod-borne viruses, which include West Nile fever virus (WNFV), a mosquito-borne virus, Rift Valley fever virus (RVFV), a mosquito-borne virus, and Crimean-Congo haemorrhagic fever virus (CCHFV), a tick-borne virus. These arthropod-borne viruses can cause disease in different domestic and wild animals and in humans, posing a threat to public health because of their epidemic and zoonotic potential. In recent decades, the geographical distribution of these diseases has expanded. Outbreaks of WNF have already occurred in Europe, especially in the Mediterranean basin. Moreover, CCHF is endemic in many European countries and serious outbreaks have occurred, particularly in the Balkans, Turkey and Southern Federal Districts of Russia. In 2000, RVF was reported for the first time outside the African continent, with cases being confirmed in Saudi Arabia and Yemen. This spread was probably caused by ruminant trade and highlights that there is a threat of expansion of the virus into other parts of Asia and Europe. In the light of global warming and globalisation of trade and travel, public interest in emerging zoonotic diseases has increased. This is especially evident regarding the geographical spread of vector-borne diseases. A multi-disciplinary approach is now imperative, and groups need to collaborate in an integrated manner that includes vector control, vaccination programmes, improved therapy strategies, diagnostic tools and surveillance, public awareness, capacity building and improvement of infrastructure in endemic regions

Sensitive detection of EBV microRNAs across cancer spectrum reveals association with decreased survival in adult acute myelocytic leukemia

Epstein Barr virus (EBV) is the etiologic agent involved in numerous human cancers. After infecting the host, EBV establishes a latent infection, with low levels of messenger RNA (mRNA) and protein expression, evolved to evade immune recognition. Conversely, EBV microRNAs (miRNA) are expressed ubiquitously and abundantly within infected cells. Their role in tumor biology and clinical outcomes across the spectrum of cancer is not fully explained. Here, we applied our bioinformatics pipeline for quantitative EBV miRNA detection to examine sequencing data of 8,955 individual tumor samples across 27 tumor types representing the breadth of cancer. We uncover an association of intermediate levels of viral miRNA with decreased survival in adult acute myeloid leukemia (AML) patients (P = 0.00013). Prognostic modeling of this association suggests that increased EBV miRNA levels represent an independent risk factor for poor patient outcomes. Furthermore, we explore differences in expression between elevated and absent viral miRNA loads in adult AML tumors finding that EBV positivity was associated with proinflammatory signals. Together, given no associations were found for pediatric AML, our analyses suggests EBV positivity has the potential for being a prognostic biomarker and might represent a surrogate measure related to immune impairment in adult patients

Presentation and Treatment Outcomes of Liberian Children Age 5 Years and Under Diagnosed With Severe Malaria

Malaria is endemic in Liberia with a prevalence rate of up to 60% in some regions, and it has been a major cause of death in children under 5 years of age. Prior to the recent Ebola epidemic, we undertook a prospective, hospital-based pilot study at the National Referral Hospital in Monrovia, to characterize the presentation, accuracy of diagnosis, and treatment outcomes of children presenting for treatment of malaria. From June 2013 to May 2014, we recruited children 5 years and under who presented to the JFK Medical Center with suspected malaria. We collected both clinical and laboratory data on admission and on discharge. We enrolled 477 patients with an average age of 1.6 years. Demographic factors associated with testing negative for malaria included regular bed net use and prior treatment for malaria. The most common presenting symptoms of severe malaria in this population were headache and seizures. Of 246 patients admitted and treated for severe malaria, 33% tested negative by rapid diagnostic test and blood smear for malaria. The case fatality rate was higher for the patients who tested negative for malaria (4.9%) versus those who tested positive (0.6%). Three children who tested negative for malaria showed evidence of undiagnosed Salmonella typhi infection. These results suggest that malaria may be overdiagnosed and that the diagnoses of other infectious diseases, which present in a similar fashion, may be neglected. These findings underscore the need to develop rapid diagnostic tests to screen for alternative causes of febrile illness

Differential Gene Expression Analysis and Clinical Correlations within Endemic Burkitt Lymphoma

Endemic Burkitt lymphoma (eBL) is the most common pediatric cancer in equatorial Africa and is associated with malaria and Epstein-Barr virus co-infections. Molecular alterations within the eBL tumor genome and transcriptome have not been adequately investigated or compared to sporadic Burkitt lymphoma (sBL). Given that eBL has distinct clinical presentations in the jaw as opposed to the abdomen which are associated with survival, we hypothesize that transcriptome sequencing (RNA-seq) and potentially underlying genetic alterations will enhance our understanding of pathogenesis. Our results compare genome-wide RNA transcript abundances between eBL tumors from children (ages 6-7 yrs) with Stage I (Jaw tumor, n=14) and Stage II (abdominal, n=24) disease from Western Kenya to previously published work analyzing sBL which present in older children residing in developed countries and that tend not to be associated with EBV. Our initial analysis confirms mutational changes with likely functional alterations in the genes ID3 and TCF3, the key regulators of oncogenic pathways implicated in BL. However, the specific mutations observed in sBL are at lower frequency within eBL cases. This work represents the first comprehensive gene expression profile analysis of different eBL tumors. Hierarchical clustering, gene ontology and pathway analysis will provide insight into pathogenesis and new targets for chemotherapy

Minimal Assumptions for Optimal Serology Classification: Theory and Implications for Multidimensional Settings and Impure Training Data

Minimizing error in prevalence estimates and diagnostic classifiers remains a challenging task in serology. In theory, these problems can be reduced to modeling class-conditional probability densities (PDFs) of measurement outcomes, which control all downstream analyses. However, this task quickly succumbs to the curse of dimensionality, even for assay outputs with only a few dimensions (e.g. target antigens). To address this problem, we propose a technique that uses empirical training data to classify samples and estimate prevalence in arbitrary dimension without direct access to the conditional PDFs. We motivate this method via a lemma that relates relative conditional probabilities to minimum-error classification boundaries. This leads us to formulate an optimization problem that: (i) embeds the data in a parameterized, curved space; (ii) classifies samples based on their position relative to a coordinate axis; and (iii) subsequently optimizes the space by minimizing the empirical classification error of pure training data, for which the classes are known. Interestingly, the solution to this problem requires use of a homotopy-type method to stabilize the optimization. We then extend the analysis to the case of impure training data, for which the classes are unknown. We find that two impure datasets suffice for both prevalence estimation and classification, provided they satisfy a linear independence property. Lastly, we discuss how our analysis unifies discriminative and generative learning techniques in a common framework based on ideas from set and measure theory. Throughout, we validate our methods in the context of synthetic data and a research-use SARS-CoV-2 enzyme-linked immunosorbent (ELISA) assay