A geometric generalization of continued fractions for imaginary quadratic fields

The Euclidean Algorithm for the integers is well known and yields a finite continued fraction expansion for each rational number. Geometrically, successive convergents in this expansion correspond to endpoints of edges in the Farey tessellation of the complex upper half plane. The sequence of convergents thus describes a path from the point at infinity to a given rational number, following edges of the tessellation; by identifying points in the upper half plane with positive definite binary quadratic forms (up to scaling), we express this path as a product of matrices in SL2(Z). In general, when the ring of integers of a quadratic number field is Euclidean, there exists a suitable Euclidean function and algorithm with which we may construct a continued fraction expansion for each field element. In these cases, we prove the analogous result that pairs of adjacent convergents determine edges in the Voronoi tessellation of hyperbolic 3-space. We identify points in the upper half space with positive definite binary Hermitian forms (up to scaling), and express the resulting path as a product of matrices in GL2(OF ). Finally, since the Voronoi tessellation exists for all imaginary quadratic fields, including those with non-Euclidean rings of integers, we explore the extent to which this geometric interpretation of continued fractions holds in the general case

Evidence for D1 Dopamine Receptor Activation by a Paracrine Signal of Dopamine in Tick Salivary Glands

Ticks that feed on vertebrate hosts use their salivary secretion, which contains various bioactive components, to manipulate the host's responses. The mechanisms controlling the tick salivary gland in this dynamic process are not well understood. We identified the tick D1 receptor activated by dopamine, a potent inducer of the salivary secretion of ticks. Temporal and spatial expression patterns examined by immunohistochemistry and reverse transcription polymerase chain reaction suggest that the dopamine produced in the basal cells of salivary gland acini is secreted into the lumen and activates the D1 receptors on the luminal surface of the cells lining the acini. Therefore, we propose a paracrine function of dopamine that is mediated by the D1 receptor in the salivary gland at an early phase of feeding. The molecular and pharmacological characterization of the D1 receptor in this study provides the foundation for understanding the functions of dopamine in the blood-feeding of ticks

Linear epitopes of Paracoccidioides brasiliensis and Other Fungal Agents of Human Systemic Mycoses As vaccine Candidates

Dimorphic fungi are agents of systemic mycoses associated with significant morbidity and frequent lethality in the Americas. Among the pathogenic species are Paracoccidioides brasiliensis and Paracoccidioides lutzii, which predominate in South AmericaHistoplasma capsulatum, Coccidioides posadasii, and Coccidioides immitis, and the Sporothrix spp. complex are other important pathogens. Associated with dimorphic fungi other important infections are caused by yeast such as Candida spp. and Cryptococcus spp. or mold such as Aspergillus spp., which are also fungal agents of deadly infections. Nowadays, the actual tendency of therapy is the development of a pan-fungal vaccine. This is, however, not easy because of the complexity of eukaryotic cells and the particularities of different species and isolates. Albeit there are several experimental vaccines being studied, we will focus mainly on peptide vaccines or epitopes of T-cell receptors inducing protective fungal responses. These peptides can be carried by antibody inducing beta-( 1,3)-glucan oligo or polysaccharides, or be mixed with them for administration. The present review discusses the efficacy of linear peptide epitopes in the context of antifungal immunization and vaccine proposition.FAPESPCAPESUniv Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, Sao Paulo, BrazilUniv Fed Sao Paulo, Inst Biomed Sci, Dept Microbiol, Sao Paulo, BrazilUniv Fed Sao Paulo, Lab Med Mycol IMTSP HCFMUSP LIM53, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, Sao Paulo, BrazilUniv Fed Sao Paulo, Inst Biomed Sci, Dept Microbiol, Sao Paulo, BrazilUniv Fed Sao Paulo, Lab Med Mycol IMTSP HCFMUSP LIM53, Sao Paulo, BrazilFAPESP: 2016/08730-6FAPESP: 2010/51423-0Web of Scienc

T-cell Subsets and Antifungal Host Defenses

It has been long appreciated that protective immunity against fungal pathogens is dependent on activation of cellular adaptive immune responses represented by T lymphocytes. The T-helper (Th)1/Th2 paradigm has proven to be essential for the understanding of protective adaptive host responses. Studies that have examined the significance of regulatory T cells in fungal infection, and the recent discovery of a new T-helper subset called Th17 have provided crucial information for understanding the complementary roles played by the various T-helper lymphocytes in systemic versus mucosal antifungal host defense. This review provides an overview of the role of the various T-cell subsets during fungal infections and the reciprocal regulation between the T-cell subsets contributing to the tailored host response against fungal pathogens

Proteome Analysis of Borrelia burgdorferi Response to Environmental Change

We examined global changes in protein expression in the B31 strain of Borrelia burgdorferi, in response to two environmental cues (pH and temperature) chosen for their reported similarity to those encountered at different stages of the organism's life cycle. Multidimensional nano-liquid chromatographic separations coupled with tandem mass spectrometry were used to examine the array of proteins (i.e., the proteome) of B. burgdorferi for different pH and temperature culture conditions. Changes in pH and temperature elicited in vitro adaptations of this spirochete known to cause Lyme disease and led to alterations in protein expression that are associated with increased microbial pathogenesis. We identified 1,031 proteins that represent 59% of the annotated genome of B. burgdorferi and elucidated a core proteome of 414 proteins that were present in all environmental conditions investigated. Observed changes in protein abundances indicated varied replicon usage, as well as proteome functional distributions between the in vitro cell culture conditions. Surprisingly, the pH and temperature conditions that mimicked B. burgdorferi residing in the gut of a fed tick showed a marked reduction in protein diversity. Additionally, the results provide us with leading candidates for exploring how B. burgdorferi adapts to and is able to survive in a wide variety of environmental conditions and lay a foundation for planned in situ studies of B. burgdorferi isolated from the tick midgut and infected animals

Biochemical Characterization and Evaluation of a Brugia malayi Small Heat Shock Protein as a Vaccine against Lymphatic Filariasis

Filarial nematodes enjoy one of the longest life spans of any human pathogen due to effective immune evasion strategies developed by the parasite. Among the various immune evasion strategies exhibited by the parasite, Interleukin 10 (IL-10) productions and IL-10 mediated immune suppression has significant negative impact on the host immune system. Recently, we identified a small heat shock protein expressed by Brugia malayi (BmHsp12.6) that can bind to soluble human IL-10 receptor alpha (IL-10R) and activate IL-10 mediated effects in cell lines. In this study we show that the IL-10R binding region of BmHsp12.6 is localized to its N-terminal region. This region has significant sequence similarity to the receptor binding region of human IL-10. In vitro studies confirm that the N-terminal region of BmHsp12.6 (N-BmHsp12.6) has IL-10 like activity and the region containing the alpha crystalline domain and C-terminus of BmHsp12.6 (BmHsp12.6αc) has no IL-10 like activity. However, BmHsp12.6αc contains B cell, T cell and CTL epitopes. Members of the sHSP families are excellent vaccine candidates. Evaluation of sera samples from putatively immune endemic normal (EN) subjects showed IgG1 and IgG3 antibodies against BmHsp12.6αc and these antibodies were involved in the ADCC mediated protection. Subsequent vaccination trials with BmHsp12.6αc in a mouse model using a heterologous prime boost approach showed that 83% protection can be achieved against B. malayi L3 challenge. Results presented in this study thus show that the N-BmHsp12.6 subunit of BmHsp12.6 has immunoregulatory function, whereas, the BmHsp12.6αc subunit of BmHsp12.6 has significant vaccine potential

Immunization with a Borrelia burgdorferi BB0172-Derived Peptide Protects Mice against Lyme Disease

Lyme disease is the most prevalent arthropod borne disease in the US and it is caused by the bacterial spirochete Borrelia burgdorferi (Bb), which is acquired through the bite of an infected Ixodes tick. Vaccine development efforts focused on the von Willebrand factor A domain of the borrelial protein BB0172 from which four peptides (A, B, C and D) were synthesized and conjugated to Keyhole Limpet Hemocyanin, formulated in Titer Max® adjuvant and used to immunize C3H/HeN mice subcutaneously at days 0, 14 and 21. Sera were collected to evaluate antibody responses and some mice were sacrificed for histopathology to evaluate vaccine safety. Twenty-eight days post-priming, protection was evaluated by needle inoculation of half the mice in each group with 103 Bb/mouse, whereas the rest were challenged with 105Bb/mouse. Eight weeks post-priming, another four groups of similarly immunized mice were challenged using infected ticks. In both experiments, twenty-one days post-challenge, the mice were sacrificed to determine antibody responses, bacterial burdens and conduct histopathology. Results showed that only mice immunized with peptide B were protected against challenge with Bb. In addition, compared to the other the treatment groups, peptide B-immunized mice showed very limited inflammation in the heart and joint tissues. Peptide B-specific antibody titers peaked at 8 weeks post-priming and surprisingly, the anti-peptide B antibodies did not cross-react with Bb lysates. These findings strongly suggest that peptide B is a promising candidate for the development of a new DIVA vaccine (Differentiate between Infected and Vaccinated Animals) for protection against Lyme disease.The open access fee for this work was funded through the Texas A&M University Open Access to Knowledge (OAK) Fund

Voices of Women in the Field: Women and Leadership

Throughout history, men have dominated leadership roles, yet women are creating a new force of energy. They are actively involved as leaders in business, health care, politics, education, and sports, as well as on economic, social, and environmental issues. This involvement of all people in leadership means that [women] will have more opportunities to lead people and develop [their] leadership skills. (Karnes & Bean, 1993, p. 130) Leadership, or the position or function of a leader; ability to lead; an act or instance of leading; guidance; direction; the leaders of a group (Dictionary.com, 2006), enables women to make societal change. Astin and Leland (1991) interviewed women leaders and noted that they are, Predisposed to leadership by their heritage, perhaps, or propelled by their special skills and talents, the women leaders also persuasively demonstrate the critical significance of experiences that allow leadership practice (p. 54). Women leaders come from all types of homes, from large cities and small cities, from varying backgrounds and experiences, but there are common themes that emerge from these leaders. As noted by Shriberg, Shriberg, and Kumari (2005), successful leadership is studied and analyzed by many people and organizations because it is difficult to understand, define, and articulate, and yet, it is one of the key elements to success of a project or organization. To better understand women and leadership, focusing on past and present successful women leaders and hearing their recommendations and suggestions will inform us

Optimal Voluntary Vaccination of Adults and Adolescents Can Help Eradicate Hepatitis B in China

Hepatitis B (HBV) is one of the most common infectious diseases, with a worldwide annual incidence of over 250 million people. About one-third of the cases are in China. While China made significant efforts to implement a nationwide HBV vaccination program for newborns, a significant number of susceptible adults and teens remain. In this paper, we analyze a game-theoretical model of HBV dynamics that incorporates government-provided vaccination at birth coupled with voluntary vaccinations of susceptible adults and teens. We show that the optimal voluntary vaccination brings the disease incidence to very low levels. This result is robust and, in particular, due to a high HBV treatment cost, essentially independent from the vaccine cost