Invitation Only Research Event

Event participants

Rebecca Wolfe, Lecturer, Harris School for Public Policy and Associate, Pearson Institute for the Study and Resolution of Global Conflicts, University of Chicago
Tom Gillhespy, Principal Consultant, Itad
Shodmon Hojibekov, Chief Executive Officer, Aga Khan Agency for Habitat (Afghanistan)
Chair: Champa Patel, Director, Asia-Pacific Programme, Chatham House

One of the most useful tools in analyzing the spread of disease is a system of evolutionary equations that reflects the dynamics among three distinct categories of a population: those susceptible (S) to a disease, those infected (I) with it, and those recovered (R) from it. This SIR model is applicable to a range of diseases, from smallpox to the flu. To predict the impact of a particular disease it is crucial to determine certain parameters associated with it, such as the average number of people that a typical infected person will infect. Researchers estimate these parameters by applying statistical methods to gathered data, which aren.t complete because, for example, some cases aren.t reported. Armed with reliable models, mathematicians help public health officials battle the complex, rapidly changing world of modern disease. Today.s models are more sophisticated than those of even a few years ago. They incorporate information such as contact periods that vary with age (young people have contact with one another for a longer period of time than do adults from different households), instead of assuming equal contact periods for everyone. The capacity to treat variability makes it possible to predict the effectiveness of targeted vaccination strategies to combat the flu, for instance. Some models now use graph theory and matrices to represent networks of social interactions, which are important in understanding how far and how fast a given disease will spread. For More Information: Mathematical Models in Population Biology and Epidemiology, Fred Brauer and Carlos Castillo-Chavez.

One of the most useful tools in analyzing the spread of disease is a system of evolutionary equations that reflects the dynamics among three distinct categories of a population: those susceptible (S) to a disease, those infected (I) with it, and those recovered (R) from it. This SIR model is applicable to a range of diseases, from smallpox to the flu. To predict the impact of a particular disease it is crucial to determine certain parameters associated with it, such as the average number of people that a typical infected person will infect. Researchers estimate these parameters by applying statistical methods to gathered data, which aren.t complete because, for example, some cases aren.t reported. Armed with reliable models, mathematicians help public health officials battle the complex, rapidly changing world of modern disease. Today.s models are more sophisticated than those of even a few years ago. They incorporate information such as contact periods that vary with age (young people have contact with one another for a longer period of time than do adults from different households), instead of assuming equal contact periods for everyone. The capacity to treat variability makes it possible to predict the effectiveness of targeted vaccination strategies to combat the flu, for instance. Some models now use graph theory and matrices to represent networks of social interactions, which are important in understanding how far and how fast a given disease will spread. For More Information: Mathematical Models in Population Biology and Epidemiology, Fred Brauer and Carlos Castillo-Chavez.

As difficult as it is to do the census, the ensuing process of determining the number of congressional seats for each state can be even harder. The basic premise, that the proportion of each state's delegation in the House should match its proportion of the U.S. population, is simple enough. The difficulty arises when deciding what to do with the fractions that inevitably arise (e.g., New York can't have 28.7 seats). Over the past 200 years, several methods of apportioning seats have been used. Many sound good but can lead to paradoxes, such as an increase in the total number of House seats actually resulting in a reduction of a state's delegation. The method used since the 1940s, whose leading proponent was a mathematician, is one that avoids such paradoxes. A natural question is Why 435 seats? Nothing in the Constitution mandates this number, although there is a prohibition against having more than one seat per 30,000 people. One model, based on the need for legislators to communicate with their constituents and with each other, uses algebra and calculus to show that the ideal assembly size is the cube root of the population it represents. Remarkably, the size of the House mirrored this rule until the early 1900s. To obey the rule now would require an increase to 670, which would presumably both better represent the population and increase the chances that the audience in the seats for those late speeches would outnumber the speaker. For More Information: "E pluribus confusion", Barry Cipra, American Scientist, July-August 2010.

As difficult as it is to do the census, the ensuing process of determining the number of congressional seats for each state can be even harder. The basic premise, that the proportion of each state's delegation in the House should match its proportion of the U.S. population, is simple enough. The difficulty arises when deciding what to do with the fractions that inevitably arise (e.g., New York can't have 28.7 seats). Over the past 200 years, several methods of apportioning seats have been used. Many sound good but can lead to paradoxes, such as an increase in the total number of House seats actually resulting in a reduction of a state's delegation. The method used since the 1940s, whose leading proponent was a mathematician, is one that avoids such paradoxes. A natural question is Why 435 seats? Nothing in the Constitution mandates this number, although there is a prohibition against having more than one seat per 30,000 people. One model, based on the need for legislators to communicate with their constituents and with each other, uses algebra and calculus to show that the ideal assembly size is the cube root of the population it represents. Remarkably, the size of the House mirrored this rule until the early 1900s. To obey the rule now would require an increase to 670, which would presumably both better represent the population and increase the chances that the audience in the seats for those late speeches would outnumber the speaker. For More Information: "E pluribus confusion", Barry Cipra, American Scientist, July-August 2010.

Researcher: Christopher Butson, Scientific Computing and Imaging Institute, University of Utah. Christopher Butson talks about work he's done to help treat Parkinson's disease.

Located in a global hotspot for biodiversity, Los Angeles County is home to more than 4,000 distinct species of plants and animals, including 52 endangered species - more than any county outside of Hawaii. And with 1 million animal and plant species facing extinction due to human activity, according to the United Nations, efforts to better understand the factors that shape biodiversity in Los Angeles could help shape global conservation efforts.

Do biodiversity losses aggravate transmission of infectious diseases spread by animals to humans? The jury is still out but several scientists say there is a "biodiversity dilution effect" in which declining biodiversity results in increased infectious-disease transmission.

Last month, I paid a visit to Yuen Long where I met a few families at Long Shin Estate. Apart from distributing face masks and anti-epidemic supplies to them, I was also given a better understanding of the impact brought by the epidemic on their daily lives. To show our concerted support in the fight against the disease, the Department of Justice (DoJ) Staff Club organised a volunteer activity on Sunday, which I joined with my fellow colleagues in offering our help to those in need.

To echo the Government's move to stay united, the DoJ Staff Club put forth a cash contribution campaign to buy anti-epidemic supplies for donation. The staff club volunteers acquired face masks and alcohol-based handrub in different ways - some were purchased through online shopping and some were bought at medicine stores. Last Sunday, I joined the volunteers in packing the anti-epidemic supplies, supermarket cash coupons and leaflets with health information. Our volunteers took the care packs in person to a non-governmental organisation a few days ago for passing to the elderly and low-income groups.

The staff club has been participating in volunteer services now and then. Given the overwhelming response this time, I am glad to know that more volunteer activities would be organised in the future. I would definitely be joining as many as I could. Through offering our efforts to help those in need, we hope to show our care for the less privileged in society and contribute to building a caring and inclusive community.

The public services of the DoJ, like all other government departments, have gradually resumed back to normal. I inspected the Justice Place on Monday to learn more about the infection control measures in place, such as the body temperature checking arrangement, provision of hand sanitisers and sanitising mats at building entrances.

We must remain vigilant as the epidemic is still severe, and more importantly, we also need to stand in solidarity in the fight against the disease.

Secretary for Justice Teresa Cheng wrote this article and posted it on her blog on March 5.

Sarah Tomasello
Jan 1, 2008; 21:19-25
Articles

Jennal L. Johnson
Jul 1, 2006; 19:148-153
Articles

Jul 1, 2002; 15:
Patient Information

Betsy B. Dokken
Jul 1, 2008; 21:160-165
From Research to Practice/Cardiovascular Disease and Diabetes

(University of Southampton) Scientists have published highly detailed images of lab-grown neurons using Extreme Ultraviolet radiation that could aid the analysis of neurodegenerative diseases.

(University of South Florida (USF Health)) A new preclinical study by researchers at the University of South Florida Health (USF Health) Morsani College of Medicine and Johns Hopkins University School of Medicine offers promise of a specific treatment for NEC, a rare inflammatory bowel disease that is a leading cause of death in premature infants. The team found that inhibiting the inflammatory and blood-clotting molecule thrombin with targeted nanotherapy can protect against NEC-like injury in newborn mice.

(University of Jyväskylä - Jyväskylän yliopisto) Researchers at the universities of Jyvaskyla and Xiamen discovered a novel way to make functional macroscopic crystalline materials out of nanometer-size 34-atom silver-gold intermetallic clusters. The cluster material has a highly anisotropic electrical conductivity, being a semiconductor in one direction and an electrical insulator in other directions. The research was published in Nature Communications on May 6, 2020.

Previous studies have shown that sphingosine kinase interacting protein (SKIP) inhibits sphingosine kinase (SK) function in fibroblasts. SK phosphorylates sphingosine producing the potent signaling molecule sphingosine-1-phosphate (S1P). SKIP gene (SPHKAP) expression is silenced by hypermethylation of its promoter in acute myeloid leukemia (AML). However, why SKIP activity is silenced in primary AML cells is unclear. Here, we investigated the consequences of SKIP down-regulation in AML primary cells and the effects of SKIP re-expression in leukemic cell lines. Using targeted ultra-HPLC-tandem MS (UPLC-MS/MS), we measured sphingolipids (including S1P and ceramides) in AML and control cells. Primary AML cells had significantly lower SK activity and intracellular S1P concentrations than control cells, and SKIP-transfected leukemia cell lines exhibited increased SK activity. These findings show that SKIP re-expression enhances SK activity in leukemia cells. Furthermore, other bioactive sphingolipids such as ceramide were also down-regulated in primary AML cells. Of note, SKIP re-expression in leukemia cells increased ceramide levels 2-fold, inactivated the key signaling protein extracellular signal-regulated kinase, and increased apoptosis following serum deprivation or chemotherapy. These results indicate that SKIP down-regulation in AML reduces SK activity and ceramide levels, an effect that ultimately inhibits apoptosis in leukemia cells. The findings of our study contrast with previous results indicating that SKIP inhibits SK function in fibroblasts and therefore challenge the notion that SKIP always inhibits SK activity.

The transcription factor forkhead box P3 (FOXP3) is a biomarker for regulatory T cells and can also be expressed in cancer cells, but its function in cancer appears to be divergent. The role of hepatocyte-expressed FOXP3 in hepatocellular carcinoma (HCC) is unknown. Here, we collected tumor samples and clinical information from 115 HCC patients and used five human cancer cell lines. We examined FOXP3 mRNA sequences for mutations, used a luciferase assay to assess promoter activities of FOXP3's target genes, and employed mouse tumor models to confirm in vitro results. We detected mutations in the FKH domain of FOXP3 mRNAs in 33% of the HCC tumor tissues, but in none of the adjacent nontumor tissues. None of the mutations occurred at high frequency, indicating that they occurred randomly. Notably, the mutations were not detected in the corresponding regions of FOXP3 genomic DNA, and many of them resulted in amino acid substitutions in the FKH region, altering FOXP3's subcellular localization. FOXP3 delocalization from the nucleus to the cytoplasm caused loss of transcriptional regulation of its target genes, inactivated its tumor-inhibitory capability, and changed cellular responses to histone deacetylase (HDAC) inhibitors. More complex FKH mutations appeared to be associated with worse prognosis in HCC patients. We conclude that mutations in the FKH domain of FOXP3 mRNA frequently occur in HCC and that these mutations are caused by errors in transcription and are not derived from genomic DNA mutations. Our results suggest that transcriptional mutagenesis of FOXP3 plays a role in HCC.

Prostate cancer (PCa) cells heavily rely on an active androgen receptor (AR) pathway for their survival. Enzalutamide (MDV3100) is a second-generation antiandrogenic drug that was approved by the Food and Drug Administration in 2012 to treat patients with castration-resistant prostate cancer (CRPC). However, emergence of resistance against this drug is inevitable, and it has been a major challenge to develop interventions that help manage enzalutamide-resistant CRPC. Erythropoietin-producing human hepatocellular (Eph) receptors are targeted by ephrin protein ligands and have a broad range of functions. Increasing evidence indicates that this signaling pathway plays an important role in tumorigenesis. Overexpression of EPH receptor B4 (EPHB4) has been observed in multiple types of cancer, being closely associated with proliferation, invasion, and metastasis of tumors. Here, using RNA-Seq analyses of clinical and preclinical samples, along with several biochemical and molecular methods, we report that enzalutamide-resistant PCa requires an active EPHB4 pathway that supports drug resistance of this tumor type. Using a small kinase inhibitor and RNAi-based gene silencing to disrupt EPHB4 activity, we found that these disruptions re-sensitize enzalutamide-resistant PCa to the drug both in vitro and in vivo. Mechanistically, we found that EPHB4 stimulates the AR by inducing proto-oncogene c-Myc (c-Myc) expression. Taken together, these results provide critical insight into the mechanism of enzalutamide resistance in PCa, potentially offering a therapeutic avenue for enhancing the efficacy of enzalutamide to better manage this common malignancy.