Functional Cellular Anti-Tumor Mechanisms are Augmented by Genetic Proteoglycan Targeting.

While recent research points to the importance of glycans in cancer immunity, knowledge on functional mechanisms is lacking. In lung carcinoma among other tumors, anti-tumor immunity is suppressed; and while some recent therapies boost T-cell mediated immunity by targeting immune-checkpoint pathways, robust responses are uncommon. Augmenting tumor antigen-specific immune responses by endogenous dendritic cells (DCs) is appealing from a specificity standpoint, but challenging. Here, we show that restricting a heparan sulfate (HS) loss-of-function mutation in the HS sulfating enzyme Ndst1 to predominantly conventional DCs (Ndst1f/f CD11cCre+ mutation) results in marked inhibition of Lewis lung carcinoma growth along with increased tumor-associated CD8+ T cells. In mice deficient in a major DC HS proteoglycan (syndecan-4), splenic CD8+ T cells showed increased anti-tumor cytotoxic responses relative to controls. Studies examining Ndst1f/f CD11cCre + mutants revealed that mutation was associated with an increase in anti-tumor cytolysis using either splenic CD8+ T cells or tumor-infiltrating (TIL) CD8+ T cells purified ex-vivo, and tested in pooled effector-to-target cytolytic assays against tumor cells from respective animals. On glycan compositional analysis, HS purified from Ndst1f/f CD11cCre + mutant DCs had reduced overall sulfation, including reduced sulfation of a tri-sulfated disaccharide species that was intriguingly abundant on wildtype DC HS. Interestingly, antigen presentation in the context of major histocompatibility complex class-I (MHC-I) was enhanced in mutant DCs, with more striking effects in the setting of HS under-sulfation, pointing to a likely regulatory role by sulfated glycans at the antigen/MHC-I - T-cell interface; and possibly future opportunities to improve antigen-specific T cell responses by immunologic targeting of HS proteoglycans in cancer

3D lithium ion batteries—from fundamentals to fabrication

3D microbatteries are proposed as a step change in the energy and power per footprint of surface mountable rechargeable batteries for microelectromechanical systems (MEMS) and other small electronic devices. Within a battery electrode, a 3D nanoarchitecture gives mesoporosity, increasing power by reducing the length of the diffusion path; in the separator region it can form the basis of a robust but porous solid, isolating the electrodes and immobilising an otherwise fluid electrolyte. 3D microarchitecture of the whole cell allows fabrication of interdigitated or interpenetrating networks that minimise the ionic path length between the electrodes in a thick cell. This article outlines the design principles for 3D microbatteries and estimates the geometrical and physical requirements of the materials. It then gives selected examples of recent progress in the techniques available for fabrication of 3D battery structures by successive deposition of electrodes, electrolytes and current collectors onto microstructured substrates by self-assembly methods

Theoretical investigation of the design and performance of a dual energy (kV and MV) radiotherapy imager

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134977/1/mp5120.pd

Cholesterol and the risk of grade-specific prostate cancer incidence: evidence from two large prospective cohort studies with up to 37 years' follow up

<b>Background</b> High cholesterol may be a modifiable risk factor for prostate cancer but results have been inconsistent and subject to potential "reverse causality" where undetected disease modifies cholesterol prior to diagnosis.<p></p> <b>Methods</b> We conducted a prospective cohort study of 12,926 men who were enrolled in the Midspan studies between 1970 and 1976 and followed up to 31st December 2007. We used Cox-Proportional Hazards Models to evaluate the association between baseline plasma cholesterol and Gleason grade-specific prostate cancer incidence. We excluded cancers detected within at least 5 years of cholesterol assay.<p></p> <b>Results</b> 650 men developed prostate cancer in up to 37 years' follow-up. Baseline plasma cholesterol was positively associated with hazard of high grade (Gleason score[greater than or equal to]8) prostate cancer incidence (n=119). The association was greatest among men in the 4th highest quintile for cholesterol, 6.1 to <6.69 mmol/l, Hazard Ratio 2.28, 95% CI 1.27 to 4.10, compared with the baseline of <5.05 mmol/l. This association remained significant after adjustment for body mass index, smoking and socioeconomic status.<p></p> <b>Conclusions</b> Men with higher cholesterol are at greater risk of developing high-grade prostate cancer but not overall risk of prostate cancer. Interventions to minimise metabolic risk factors may have a role in reducing incidence of aggressive prostate cancer

Ultrafast optical switching using parity-time symmetric Bragg gratings

This paper reports on time-domain modeling of an optical switch based on the parity–time (PT) symmetric Bragg grating. The switching response is triggered by suddenly switching on the gain in the Bragg grating to create a PT-symmetric Bragg grating. Transient and dynamic behaviors of the PT Bragg gratings are analyzed using the time-domain numerical transmission line modeling method including a simple gain saturation model. The on/off ratio and the switching time of the PT Bragg grating optical switch are analyzed in terms of the level of gain introduced in the system and the operating frequency. The paper also discusses the effect the gain saturation has on the operation of the PT-symmetric Bragg gratings

Development of Degradable, pH‐Sensitive Star Vectors for Enhancing the Cytoplasmic Delivery of Nucleic Acids

The report describes the synthesis of degradable, pH‐sensitive, membrane‐destabilizing, star‐shaped polymers where copolymers of hydrophobic hexyl methacrylate (HMA) and 2‐(dimethylamino)ethyl methacrylate (DMAEMA) monomers are grafted from the secondary face of a beta‐cyclodextrin (β‐CD) core via acid‐labile hydrazone linkages using atom transfer radical polymerization. The effect of the graft's molecular weight, HMA/DMAEMA molar ratio, and the fraction of DMAEMA converted to cationic N,N,N‐trimethylaminoethyl methacrylate (TMAEMA) monomers on polymer's transfection capacity is systematically investigated. Results show that all star‐shaped polymers condense anti‐GAPDH silencing RNA (siRNA) into nanosized particles at +/‐ ratio ≤ 4:1. Star polymers with shorter (25kDa) P(HMA‐ co ‐DMAEMA‐ co ‐TMAEMA) grafts are more efficient and less cytotoxic than carriers with longer (40kDa) grafts. The results show that increasing the ratio of hydrophobic HMA monomers in graft's composition higher than 50 mole% dramatically reduces polymer's aqueous solubility and abolishes their transfection capacity. Further, retention of DMAEMA monomers in graft's composition provide a buffering capacity that enhanced the endosomal escape and transfection capacity of the polymers. These systematic studies show that β‐CD‐P(HMA‐ co ‐DMAEMA‐ co ‐TMAEMA) 4.8 polymer with a 25 kDa average graft's molecular weight and a 50/25/25 ratio of HMA/DMAEMA/TMAEMA monomers is the most efficient carrier in delivering the siRNA cargo into the cytoplasm of epithelial cancer cells. A series of degradable, pH‐sensitive, membrane‐destabilizing, star‐shaped polymers is synthesized. Star polymers are engineered to “sense” the drop in endosomal pH, which triggers the hydrolysis of acid‐labile hydrazone linkages and release of membrane‐active grafts that rupture the endosomal membrane and release the loaded siRNA cargo into the cytoplasm to produce the desired knockdown of targeted gene expression at both the mRNA and protein levels.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99666/1/3885_ftp.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99666/2/adfm_201203762_sm_suppl.pd

Screenwriting as a mode of research, and the screenplay as a research artefact

Screenwriting practice is now a flourishing mode of research within universities internationally, whereby the act of writing a screenplay or developing screenplay works is not only understood, but also celebrated as a legitimate form of knowledge discovery and dissemination. The resulting work of this creative practice research, which we might call the 'academic screenplay', thus functions simultaneously as a method of research enquiry and a 'non traditional' research artefact. In this chapter we explore what it means to develop and write a screenplay in the academy, under the conditions of and for research. By positioning screenwriting alongside and in between the disciplines of creative writing and screen production, we reflect on how it can draw from both disciplines at different times and for different purposes, and can be influenced by their specific - and sometimes contradictory - discourses. By doing so, the chapter provides a comprehensive overview of screenwriting as a growing mode of research, and its practice as an important addition to the academy

An Analysis of Factors Associated with Drug Use in Schools in The City of Ouagadougou in 2019

Faced with this situation, a general awareness has led to the creation of an international day against drug abuse and trafficking on June 26. Several international and regional conventions are working together to develop strategies and policies to fight this scourge. The aim of this study is to look for the prevalence and associated factors of drug use in schools in the city of Ouagadougou in 2019. This study used a descriptive and analytical cross-sectional study using a self-administered questionnaire administered to students in schools in the city of Ouagadougou who were present during the survey in March 2019. The collection tool was a self-administered questionnaire inspired by the WHO guide on school health surveillance in the Burkinabe context, which had been previously tested. Kobocollect software was used to collect the data. Data processing and analysis were carried out using STATA version 15.1 software. The variable of interest was drug use. The data collected were analyzed with STATA version 15.1 software. The students in this study ranged in age from 12 to 25, with a mean age of 14.78 ± 2.26 years. The prevalence of drug use was 6.11%. It varied significantly according to gender, pocket money, and history of drug use. Strategies to combat drug use must be strengthened and adapted to our context in order to bring about a change in behavior, especially in schools

Tension-type headache and sleep apnea in the general population

The main objective of this study is to investigate the relationship between tension-type headache and obstructive sleep apnea in the general population. The method involves a cross-sectional population-based study. A random age and gender stratified sample of 40,000 persons aged 20–80 years residing in Akershus, Hedmark or Oppland County, Norway were drawn by the National Population Register. A postal questionnaire containing the Berlin Questionnaire was used to classify respondents to be of either high or low risk of obstructive sleep apnea. Included in this study were 297 persons with high risk and 134 persons with low risk of sleep apnea, aged 30–65 years. They underwent an extensive clinical interview, a physical and a neurological examination by physicians, and in-hospital polysomnography. Those with apnea hypopnoea index (AHI) ≥5 were classified with obstructive sleep apnea. Tension-type headache was diagnosed according to the International Classification of Headache Disorders. Results showed the prevalence of frequent and chronic tension-type headache was 18.7 and 2.1% in the participants with obstructive sleep apnea. The logistic regression analyses showed no significant relationship between tension-type headache and obstructive sleep apnea, with adjusted odds ratios for frequent tension-type headache of 0.95 (0.55–1.62) and chronic tension-type headache of 1.91 (0.37–9.85). The results did not change when using cut-off of moderate (AHI ≥15) and severe (AHI ≥30) obstructive sleep apnea. Thus, we did not find any significant relationship between tension-type headache and the AHI. The presence and severity of sleep apneas seem not to influence presence and attack-frequency of tension-type headache in the general population