Narrow Results

The model of de Boer, Segel and Perelson, where the various shapes of antibodies are represented by sites on a d-dimensional lattice and where the antibody concentrations change with time only by constant factors, is simulated in one to ten dimensions, with millions of sites. The algorithm is fully vectorized in spite of the many if-conditions which allow one program to deal with all dimensions d. We find that an initially localized perturbation may spread over the whole lattice in high dimensions but prefers to remain localized in low dimensions.

Simulations with 10⁹ cells are made on an iPSC Hypercube with 32 parallel i860 processors, updating more than a million sites per second and per processor. This size reaches into the size range of natural immune systems. Smaller sizes are simulated in higher dimensions up to ten. These cellular automata due to de Boer. van der Laan, and Hogeweg model the idiotypic shape space and differ from usual Ising models through interactions with the mirror sites of the lattice. For majority rules (voter rules) we find Ising-like behavior with a spontaneous magnetization vanishing at some critical temperature which approaches its mean field value for high dimensions. The previously observed self-organization in the form of domain formation is thus explained as spinodal decomposition.

The high-dimensional shape space for the antibodies of the immune system is simulated with an Ising-like interaction. However, instead of the molecular field being linear in the sum of the neighbor spins, we take it as quadratic and negative. In this way the bell-shaped response curve of biological immune systems is approximated, as a probabilistic generalization of window automata. We find phase transitions only in five and more dimensions, not in two to four, for nearest-neighbor interactions.

Stauffer⁷ has replaced the window automata rules — applied by de Boer, Segel and Perelson² for simulating the immunological shape space — by probabilistic rules, very similar to the ones of the ferromagnetic Ising Model. Based on this model, we extend the interaction range to more than nearest neighbors and find phase transitions not only in higher dimensions, but also in two dimensions, Biologically these phase transitions correspond to a transition from a reasonable to a non-reasonable behavior of the whole immune network.

Thirty-nine women of reproductive age suffering from chronic pelvic inflammatory disease (PID) for at least two years, previously treated pharmacologically with no effect, were enrolled in a four-week therapeutic protocol consisting of 12 acupuncture treatments performed with the frequency of three per week. In each female patient at baseline and after the study, pain score and the following parameters in blood serum were evaluated: concentration of immunoglobulin M (IgM), albumins, α₁-globulins, α₂-globulins and γ-globulins, erythrocyte sedimentation rate (ESR) and white blood cell (WBC) count. During the study, we obtained a significant drop in ESR and IgM levels together with a rise in γ-globulin concentrations. A significant decrease (from 4.89 ± 0.82 to 0.63 ± 1.05) in pain score was obtained. The other parameters remained unchanged. These results suggest that acupuncture treatment of PID exhibits a clear anti-inflammatory and immunocompetent effect.

This paper deals with the competition between the immune system and an agressive host such as tumor. We are particularly interested in the asymptotic behavior of the system when the time goes to infinity: we prove that this competition will absolutely finish either by the suppression of the harmful substances or by the inhibition of the immune system. The model which we introduce is suitable to describe the disease evolution for a long time scale, because it takes the capacity of the body to repair cells damage into account: body cells produce new cells to replace dead ones. We also examine the evolution of the solutions if we assume that the immune system has a normal healthy state that it always tries to reach.

The TH1/TH2 paradigm has been largely used in the interpretation of several diseases, particularly in leishmaniasis. As far as we know there is no mathematical description of this model related to leishmaniasis. We have extended and modified a previous published set of equations¹ in order to adapt it to leishmanial disease particularities. The main modifications were: (1) the analysis of logistic and exponential parasite growth curves, (2) the assumption of the TH2 arm of the immune response having a positive action on parasite growth. The set of three simultaneous differential equations describing the TH1 arm, TH2 arm and parasite growth were analyzed for conditions of existence and stability of the solutions.

Stable solutions valid for the logistic and exponential parasite growth models, with its possible clinical correlations, were obtained in the following situations: (1) parasite and TH2 extinction [TH1 cure], (2) parasite extinction and TH1/TH2 co-existence [TH1/TH2 cure], (3) TH1 and parasite co-existence, TH2 extinction [stable TH1 infection], and (4) TH1, TH2 and parasite co-existence [stable TH1/TH2 infection]. TH2 and parasite co-existence associated to TH1 extinction [stable TH2 infection] was obtained only with the logistic growth model. The model also provides an alternative hypothesis for TH1 bias in resistant mice and emphazises the importance of natural immunity for the existence of chronic states.

This article summarizes the center for Molecular Medicine's research programs including regenerative medicine, immunology, virology, Singapore Oncogenome program, epithelial biology and genetic medicine.

Immunology Research in Singapore Intensifies with Official Inauguration of the Singapore Immunology Network (SIgN).

First of Its Kind in Asia — Smart Pharmaceutical Tracking and Management System.

World Courier Expands Storage Capabilities in India as Clinical Trials Boom.

WHO Warns Asian Countries of Increasing HIV and TB Coinfection.

Singapore Science at US Science Meetings.

AUSTRALIA – Chronic pain research delves into the brain

KOREA – STC life, Ltd. successfully treats stroke patients at Stem Cell Research Treatment Center

MALAYSIA – Indigenous people ‘at graver risk’ of neglected diseases

SINGAPORE – A*STAR scientists create stem cells from a drop of blood

THE PHILIPPINES – ‘Too many exotic species’ in Philippine greening plan

AFRICA – The parasite that escaped out of Africa

CANADA – Genome British Columbia researchers closing in on chlamydia vaccine

EUROPE – Teesside University pioneering life-saving research

EUROPE – Inactivated polio vaccines broadly available for the world's children in the drive toward polio eradication

EUROPE – Vitamin D deficiency may compromise immune function

EUROPE – Inflammation mobilizes tumor cells

NEPAL – Animal-borne parasites plague Nepal

UNITED STATES – Zebrafish discovery may shed light on human kidney function

UNITED STATES – Nanoparticles and magnetic fields train immune cells to fight cancer in mice

UNITED STATES – Building heart tissue that beats

UNITED STATES – Immunology researchers uncover pathways that direct immune system to turn ‘on’ or ‘off’

UNITED STATES – How diabetes drugs may work against cancer

UNITED STATES – Study reveals how a protein common in cancers jumps anti-tumor mechanisms

How the largest birds on Earth and their strong immune systems lead to a breakthrough in antibody technology research.

The following topics are under this section:

• Empowering Communities Key to Reaching Universal Health Goals
• Precision Medicine Using Innovative Biotherapeutics

Turkey coronavirus (TCoV) causes acute atrophic enteritis and uneven flock growth in turkey farms leading to economic loss. Since 1990's, turkey flocks have kept experiencing coronaviral enteritis sporadically in the United States, Canada, Europe, and Brazil. Poult enteritis and mortality syndrome (PEMS) caused by the co-infection of TCoV, astrovirus, and other viruses or bacteria resulted in significantly high mortality. Diagnosis of TCoV depends on reverse transcription polymerase chain reaction (RT-PCR), quantitative real-time PCR, immunohistochemistry (IHC), immunofluorescent antibody assay and virus isolation (VI). Genomic organization of TCoV is as follows: 5′ UTR-1a-1b-S-3a-3b-E-M-5a-5b-N-UTR 3′. Genomic analysis suggests the emergence of TCoV from infectious bronchitis virus (IBV) through the recombination of spike (S) gene. Both TCoV and IBV belong to species Avian coronavirus in genus Gammacoronavirus and have a single stranded RNA genome with a size about 27 kb. High similarity of S genes has been found between TCoV isolates in contrast to low similarity between IBV strains. TCoV infection induced strong humoral and cellular immune responses, characterized by high levels of antibody and interferon gamma. The fragment containing neutralizing epitopes in the S protein has been identified. Vaccines conferring protection against TCoV have not been developed and used in the fields but live attenuated, killed, DNA, and fowlpox virus vectored vaccines have been generated and their efficacies were evaluated. Molecular epidemiology of TCoV in recent outbreaks sheds more information on the evolution and transmission of TCoV, which will aid in developing effective vaccines or treatment to prevent, control, or eliminate TCoV infection.

In this paper, we present a competition model of malignant tumor growth that includes the immune system response. The model considers two populations: immune system (effector cells) and population of tumor (tumor cells). Ordinary differential equations are used to model the system to take into account the delay of the immune response. The existence of positive solutions of the model (with/without delay) is showed. We analyze the stability of the possible steady states with respect to time delay and the existence of positive solutions of the model (with and without delay). We show theoretically and through numerical simulations that periodic oscillations may arise through Hopf bifurcation. An algorithm for determining the stability of bifurcating periodic solutions is proved.

In this paper, I continue the study of the mathematical models presented in [J. C. Larsen, Models of cancer growth, J. Appl. Math. Comput.53(1–2) (2015) 613–645] and [J. C. Larsen, The bistability theorem in a model of metastatic cancer, to appear in Appl. Math.]. I shall prove the bistability theorem for the ODE model from [Larsen, 2015]. It is a mass action kinetic system in the variables $C$ cancer, GF growth factor and GI growth inhibitor. This theorem says that for some values of the parameters, there exist two positive singular points $c_{\ast }^{+}=(C_{\ast }^{+},{\mathrm{\text{GF}}}_{\ast },{\mathrm{\text{GI}}}_{\ast }^{+})$, $c_{\ast }^{-}=(C_{\ast }^{-},{\mathrm{\text{GF}}}_{\ast },{\mathrm{\text{GI}}}_{\ast }^{-})$ of the vector field. Here $C_{\ast }^{-}<C_{\ast }^{+}$ and $c_{\ast }^{-}$ is stable and $c_{\ast }^{+}$ is unstable, see Sec. 2. There is also a discrete model in [Larsen, 2015], it is a linear map ($T$) on three-dimensional Euclidean vector space with variables $(C,\mathrm{\text{GF}},\mathrm{\text{GI}}),$ where these variables have the same meaning as in the ODE model above. In [Larsen, 2015], I showed that one can sometimes find affine vector fields on three-dimensional Euclidean vector space whose time one map is $T$. I shall also show this in the present paper in a more general setting than in [Larsen, 2015]. This enables me to find an expression for the rate of change of cancer growth on the coordinate hyperplane $C=0$ in Euclidean vector space. I also present an ODE model of cancer metastasis with variables $C,C_M,\mathrm{\text{GF}},\mathrm{\text{GI}},$ where $C$ is primary cancer and $C_M$ is metastatic cancer and GF, GI are growth factors and growth inhibitors, respectively.

Mesenchymal stem cells (MSCs) can be isolated from many different tissue sources and have several superior characteristics that render them more ideal for therapeutic application compared to other types of stem cells. MSCs have excellent immune-modulatory properties for reducing local and systemic inflammation. MSCs modulate the immune system by secreting paracrine factors and direct cell-to-cell contact with immune cells. MSCs interact with multiple immune cells, including T-cells, B-cells, natural killer cells, macrophages and dendritic cells to modulate the host immune response. Due to their ability to suppress inflammation, preclinical and clinical studies have investigated MSCs extensively for treating autoimmune and inflammatory diseases such as multiple sclerosis, systemic lupus erythematosus, diabetes mellitus, graft-versus-host disease, and graft rejection. Thus far, most studies have reported that MSC therapy yields positive results in ameliorating immune-mediated diseases. Both autologous and allogeneic MSCs can be transplanted into humans safely without eliciting the host immune response and with minimal risk of tumor formation. However, a few limitations such as dosage, route, number, and timing of transplantation require more extensive study to derive the maximum therapeutic effect.

Natural killer (NK) cells have increasingly become a target of interest for immunotherapies. NK cells express killer immunoglobulin-like receptors (KIRs), which play a vital role in immune response to tumors by detecting cellular abnormalities. The genomic region encoding the 16 KIR genes displays high polymorphic variability in human populations, making it difficult to resolve individual genotypes based on next generation sequencing data. As a result, the impact of polymorphic KIR variation on cancer phenotypes has been understudied. Currently, labor-intensive, experimental techniques are used to determine an individual’s KIR gene copy number profile. Here, we develop an algorithm to determine the germline copy number of KIR genes from whole exome sequencing data and apply it to a cohort of nearly 5000 cancer patients. We use a k-mer based approach to capture sequences unique to specific genes, count their occurrences in the set of reads derived from an individual and compare the individual’s k-mer distribution to that of the population. Copy number results demonstrate high concordance with population copy number expectations. Our method reveals that the burden of inhibitory KIR genes is associated with survival in two tumor types, highlighting the potential importance of KIR variation in understanding tumor development and response to immunotherapy.