The work focuses on the study of hybrid mechanical systems under unilateral constraints on the po... more The work focuses on the study of hybrid mechanical systems under unilateral constraints on the position. The problem of robust control of mechanical systems is addressed under unilateral constraints by designing a nonlinear H-infinity -controller developed in the nonsmooth setting, covering impact phenomena. Performance issues of the nonlinear H-infinity-tracking controller are illustrated in a numerical simulation.
approved by: Dr. Yury Orlov Thesis Co-Director Dr. Yannick Aoustin Thesis Co-Director The primary... more approved by: Dr. Yury Orlov Thesis Co-Director Dr. Yannick Aoustin Thesis Co-Director The primary concern of the work is robust control of hybrid mechanical systems under unilateral constraints of co-dimension one. Sufficient conditions for a local solution of the underlying H∞ control problem to exist are given in terms of the appropriate solvability of Hamilton–Jacobi–Isaacs partial differential inequalities, coupled to an extra condition on the plant reset in the closed-loop. Nonlinear H∞ output feedback synthesis is thus developed in the hybrid setting, covering collision phenomena. First, the regulation and orbital stabilization of a simple pendulum, impacting a barrier, illustrate the capability of the proposed approach via position feedback design. A reference model for such an illustration is designed by performing a bifurcation study for a hybrid modification of the popular Van der Pol oscillator, using the well-known method of Poincaré sections, and determining the set of ...
The work focuses on the state feedback synthesis of hybrid mechanical systems under unilateral co... more The work focuses on the state feedback synthesis of hybrid mechanical systems under unilateral constraints. The problem of robust control of mechanical systems is addressed under unilateral constraints by designing a nonlinear state feedback H-infinity-controller developed in the hybrid setting, covering impact phenomena. Performance issues of the developed nonlinear H-infinty-tracking controller are illustrated with numerical tests on a seven-link biped robot.
HPV E5 is an oncoprotein mainly expressed in premalignant lesions, which makes it an important ta... more HPV E5 is an oncoprotein mainly expressed in premalignant lesions, which makes it an important target for a vaccine to prevent or cure cervical cancer (CC). In this study, we evaluated whether E5 targeted to DEC-205, present in dendritic cells (DCs), could induce a therapeutic protection against HPV16-induced tumor cells in a mouse model. The HPV-16 E5 (16E5) protein was cross-linked to a monoclonal antibody (mAb) specific to mouse DEC-205 (anti-DEC-205:16E5) or to an isotype control mAb (isotype:16E5). Rotavirus VP6 was cross-linked to the mouse anti-DEC-205 mAb (anti-DEC-205:VP6) as a non-specific antigen control. BALB/c mice were inoculated subcutaneously (s.c.) with the 16E5-expressing BMK-16/myc tumor cells, and 7 and 14 days later the mice were immunized s.c. with the conjugates, free 16E5 or PBS in the presence of adjuvant. Tumor growth was monitored to evaluate protection. A strong protective immune response against the tumor cells was induced when the mice were inoculated w...
Protected areas (PAs) are one of the main strategies to preserve tropical biodiversity. However, ... more Protected areas (PAs) are one of the main strategies to preserve tropical biodiversity. However, their viability is compromised by the impacts of a variety of threats. To gain a more integrated view of how different threats affect them, individually and in combination, we analyzed the spatial distribution of forest loss (2010–2015), human density, incidence of fires, and mining activities in four PAs (Cordón Pico Loro-Paxtal: CPL, El Triunfo Biosphere Reserve: ETBR, La Sepultura Biosphere Reserve: SEBR and La Frailescana: LF) located in the biodiversity stronghold of the Sierra Madre de Chiapas (SMC), Mexico. We integrated these threats in a Human Pressure Index (HPI, ranging from 0 to 1, where 1 is the highest human pressure). We found that the SEBR and LF were affected mainly by forest loss (13.43% and 11.67% forest area lost, respectively) and fire incidence (between 0.02-0.73 and 0–0.81 fire hotspots/km2, respectively). On the other hand, the ETBR and CPL had lower forest loss a...
Immunotherapy has improved the clinical response in melanoma patients, although a relevant percen... more Immunotherapy has improved the clinical response in melanoma patients, although a relevant percentage of patients still cannot be salvaged. The search for the immune populations that provide the best tumor control and that can be coaxed by immunotherapy strategies is a hot topic in cancer research nowadays. Tumor-infiltrating TCF-1+ progenitor exhausted CD8+ T cells seem to grant the best melanoma prognosis and also efficiently respond to anti-PD-1 immunotherapy, giving rise to a TIM-3+ terminally exhausted population with heightened effector activity. We tested Porins from Salmonella Typhi as a pathogen associated molecular pattern adjuvant of natural or model antigen in prophylactic and therapeutic immunization approaches against murine melanoma. Porins induced protection against melanomas, even upon re-challenging of tumor-free mice. Porins efficiently expanded IFN-γ-producing CD8+ T cells and induced central and effector memory in lymph nodes and tissue-resident (Trm) T cells in the skin and tumors. Porins induced TCF-1+ PD-1+ CD8+ Trm T cells in the tumor stroma and the presence of this population correlated with melanoma growth protection in mice. Porins immunization also cooperated with anti-PD-1 immunotherapy to hamper melanoma growth. Importantly, the potentially protective Trm populations induced by Porins in the murine model were also observed in melanoma patients in which their presence also correlated with disease control. Our data support the use of cancer vaccination to sculpt the tumor stroma with efficient and lasting Trm T cells with effector activities, highlighting the use of Porins as an adjuvant. Furthermore, our data place CD8+ Trm T cells with a progenitor exhausted phenotype as an important population for melanoma control, either independently or in cooperation with anti-PD-1 immunotherapy.
CD4 T cells are major players in the immune response against several diseases; including AIDS, le... more CD4 T cells are major players in the immune response against several diseases; including AIDS, leishmaniasis, tuberculosis, influenza and cancer. Their activation has been successfully achieved by administering antigen coupled with antibodies, against DC-specific receptors in combination with adjuvants. Unfortunately, most of the adjuvants used so far in experimental models are unsuitable for human use. Therefore, human DC-targeted vaccination awaits the description of potent, yet nontoxic adjuvants. The nontoxic cholera B subunit (CTB) can be safely used in humans and it has the potential to activate CD4 T cell responses. However, it remains unclear whether CTB can promote DC activation and can act as an adjuvant for DC-targeted antigens. Here, we evaluated the CTB's capacity to activate DCs and CD4 T cell responses, and to generate long-lasting protective immunity. Intradermal (i.d.) administration of CTB promoted late and prolonged activation and accumulation of skin and lymp...
Neonates have an increased susceptibility to infections, particularly those caused by intracellul... more Neonates have an increased susceptibility to infections, particularly those caused by intracellular pathogens, leading to high morbidity and mortality rates. This is partly because of a poor response of neonatal CD4 T cells, leading to deficient antibody production and a low production of IFN-γ, resulting in deficient elimination of intracellular pathogens. The poor memory response of human neonates has underpinned the need for improving vaccine formulations. Molecular adjuvants that improve the response of neonatal lymphocytes, such as the ligands of toll-like receptors (TLRs), are attractive candidates. Among them, flagellin, the TLR5 ligand, is effective at very low doses; prior immunity to flagellin does not impair its adjuvant activity. Human CD4 and CD8 T cells express TLR5. We found that flagellin induces the expression of IFN-γ, IL-1β and IL-12 in mononuclear cells from human neonate and adult donors. When human naïve CD4 T cells were activated in the presence of flagellin, ...
Baird´s tapir (Tapirus bairdii) is one of the most emblematic mammalian species from Mesoamerica.... more Baird´s tapir (Tapirus bairdii) is one of the most emblematic mammalian species from Mesoamerica. Due to its level of evolutionary distinctiveness and anthropogenic threat this species was recently ranked in 34th position, in terms of its urgency for conservation, among more than 4,000 species of mammals assessed by experts from the Zoological Society of London. Despite its evolutionary and conservation relevance there remain important gaps in knowledge of the basic ecology of this species. Based on camera-trapping data, we estimated Baird´s tapir abundance and analyzed its patterns of daily activity and preference for different altitude intervals in El Triunfo Biosphere reserve, one of the last strongholds for this species in southern Mexico. We also applied a recently developed method (Random encounter model) to estimate tapir density without the need of individual identification. Tapir relative abundance was: 1.3 events/100 camera-trapdays and density: 0.12 ind./km2. Tapir activi...
Hispanics who speak Spanish are at risk for low health literacy. We evaluated Spanish language hy... more Hispanics who speak Spanish are at risk for low health literacy. We evaluated Spanish language hypertension (HTN) and diabetes mellitus (DM) patient education materials from U.S. federal agency public sector sources using the Suitability of Assessment (SAM) instrument. Mean readability for HTN materials was grade 7.9 and for DM materials was grade 6.6. Mean SAM score for HTN materials was 43.9 and for DM materials was 63.2. SAM scores were significantly better for DM than for HTN materials in overall score, content, graphics, layout, stimulation/motivation, and cultural appropriateness (p < .05). Clinicians should evaluate suitability of Spanish language HTN and DM materials that they use in patient teaching.
The work focuses on the study of hybrid mechanical systems under unilateral constraints on the po... more The work focuses on the study of hybrid mechanical systems under unilateral constraints on the position. The problem of robust control of mechanical systems is addressed under unilateral constraints by designing a nonlinear H-infinity -controller developed in the nonsmooth setting, covering impact phenomena. Performance issues of the nonlinear H-infinity-tracking controller are illustrated in a numerical simulation.
approved by: Dr. Yury Orlov Thesis Co-Director Dr. Yannick Aoustin Thesis Co-Director The primary... more approved by: Dr. Yury Orlov Thesis Co-Director Dr. Yannick Aoustin Thesis Co-Director The primary concern of the work is robust control of hybrid mechanical systems under unilateral constraints of co-dimension one. Sufficient conditions for a local solution of the underlying H∞ control problem to exist are given in terms of the appropriate solvability of Hamilton–Jacobi–Isaacs partial differential inequalities, coupled to an extra condition on the plant reset in the closed-loop. Nonlinear H∞ output feedback synthesis is thus developed in the hybrid setting, covering collision phenomena. First, the regulation and orbital stabilization of a simple pendulum, impacting a barrier, illustrate the capability of the proposed approach via position feedback design. A reference model for such an illustration is designed by performing a bifurcation study for a hybrid modification of the popular Van der Pol oscillator, using the well-known method of Poincaré sections, and determining the set of ...
The work focuses on the state feedback synthesis of hybrid mechanical systems under unilateral co... more The work focuses on the state feedback synthesis of hybrid mechanical systems under unilateral constraints. The problem of robust control of mechanical systems is addressed under unilateral constraints by designing a nonlinear state feedback H-infinity-controller developed in the hybrid setting, covering impact phenomena. Performance issues of the developed nonlinear H-infinty-tracking controller are illustrated with numerical tests on a seven-link biped robot.
HPV E5 is an oncoprotein mainly expressed in premalignant lesions, which makes it an important ta... more HPV E5 is an oncoprotein mainly expressed in premalignant lesions, which makes it an important target for a vaccine to prevent or cure cervical cancer (CC). In this study, we evaluated whether E5 targeted to DEC-205, present in dendritic cells (DCs), could induce a therapeutic protection against HPV16-induced tumor cells in a mouse model. The HPV-16 E5 (16E5) protein was cross-linked to a monoclonal antibody (mAb) specific to mouse DEC-205 (anti-DEC-205:16E5) or to an isotype control mAb (isotype:16E5). Rotavirus VP6 was cross-linked to the mouse anti-DEC-205 mAb (anti-DEC-205:VP6) as a non-specific antigen control. BALB/c mice were inoculated subcutaneously (s.c.) with the 16E5-expressing BMK-16/myc tumor cells, and 7 and 14 days later the mice were immunized s.c. with the conjugates, free 16E5 or PBS in the presence of adjuvant. Tumor growth was monitored to evaluate protection. A strong protective immune response against the tumor cells was induced when the mice were inoculated w...
Protected areas (PAs) are one of the main strategies to preserve tropical biodiversity. However, ... more Protected areas (PAs) are one of the main strategies to preserve tropical biodiversity. However, their viability is compromised by the impacts of a variety of threats. To gain a more integrated view of how different threats affect them, individually and in combination, we analyzed the spatial distribution of forest loss (2010–2015), human density, incidence of fires, and mining activities in four PAs (Cordón Pico Loro-Paxtal: CPL, El Triunfo Biosphere Reserve: ETBR, La Sepultura Biosphere Reserve: SEBR and La Frailescana: LF) located in the biodiversity stronghold of the Sierra Madre de Chiapas (SMC), Mexico. We integrated these threats in a Human Pressure Index (HPI, ranging from 0 to 1, where 1 is the highest human pressure). We found that the SEBR and LF were affected mainly by forest loss (13.43% and 11.67% forest area lost, respectively) and fire incidence (between 0.02-0.73 and 0–0.81 fire hotspots/km2, respectively). On the other hand, the ETBR and CPL had lower forest loss a...
Immunotherapy has improved the clinical response in melanoma patients, although a relevant percen... more Immunotherapy has improved the clinical response in melanoma patients, although a relevant percentage of patients still cannot be salvaged. The search for the immune populations that provide the best tumor control and that can be coaxed by immunotherapy strategies is a hot topic in cancer research nowadays. Tumor-infiltrating TCF-1+ progenitor exhausted CD8+ T cells seem to grant the best melanoma prognosis and also efficiently respond to anti-PD-1 immunotherapy, giving rise to a TIM-3+ terminally exhausted population with heightened effector activity. We tested Porins from Salmonella Typhi as a pathogen associated molecular pattern adjuvant of natural or model antigen in prophylactic and therapeutic immunization approaches against murine melanoma. Porins induced protection against melanomas, even upon re-challenging of tumor-free mice. Porins efficiently expanded IFN-γ-producing CD8+ T cells and induced central and effector memory in lymph nodes and tissue-resident (Trm) T cells in the skin and tumors. Porins induced TCF-1+ PD-1+ CD8+ Trm T cells in the tumor stroma and the presence of this population correlated with melanoma growth protection in mice. Porins immunization also cooperated with anti-PD-1 immunotherapy to hamper melanoma growth. Importantly, the potentially protective Trm populations induced by Porins in the murine model were also observed in melanoma patients in which their presence also correlated with disease control. Our data support the use of cancer vaccination to sculpt the tumor stroma with efficient and lasting Trm T cells with effector activities, highlighting the use of Porins as an adjuvant. Furthermore, our data place CD8+ Trm T cells with a progenitor exhausted phenotype as an important population for melanoma control, either independently or in cooperation with anti-PD-1 immunotherapy.
CD4 T cells are major players in the immune response against several diseases; including AIDS, le... more CD4 T cells are major players in the immune response against several diseases; including AIDS, leishmaniasis, tuberculosis, influenza and cancer. Their activation has been successfully achieved by administering antigen coupled with antibodies, against DC-specific receptors in combination with adjuvants. Unfortunately, most of the adjuvants used so far in experimental models are unsuitable for human use. Therefore, human DC-targeted vaccination awaits the description of potent, yet nontoxic adjuvants. The nontoxic cholera B subunit (CTB) can be safely used in humans and it has the potential to activate CD4 T cell responses. However, it remains unclear whether CTB can promote DC activation and can act as an adjuvant for DC-targeted antigens. Here, we evaluated the CTB's capacity to activate DCs and CD4 T cell responses, and to generate long-lasting protective immunity. Intradermal (i.d.) administration of CTB promoted late and prolonged activation and accumulation of skin and lymp...
Neonates have an increased susceptibility to infections, particularly those caused by intracellul... more Neonates have an increased susceptibility to infections, particularly those caused by intracellular pathogens, leading to high morbidity and mortality rates. This is partly because of a poor response of neonatal CD4 T cells, leading to deficient antibody production and a low production of IFN-γ, resulting in deficient elimination of intracellular pathogens. The poor memory response of human neonates has underpinned the need for improving vaccine formulations. Molecular adjuvants that improve the response of neonatal lymphocytes, such as the ligands of toll-like receptors (TLRs), are attractive candidates. Among them, flagellin, the TLR5 ligand, is effective at very low doses; prior immunity to flagellin does not impair its adjuvant activity. Human CD4 and CD8 T cells express TLR5. We found that flagellin induces the expression of IFN-γ, IL-1β and IL-12 in mononuclear cells from human neonate and adult donors. When human naïve CD4 T cells were activated in the presence of flagellin, ...
Baird´s tapir (Tapirus bairdii) is one of the most emblematic mammalian species from Mesoamerica.... more Baird´s tapir (Tapirus bairdii) is one of the most emblematic mammalian species from Mesoamerica. Due to its level of evolutionary distinctiveness and anthropogenic threat this species was recently ranked in 34th position, in terms of its urgency for conservation, among more than 4,000 species of mammals assessed by experts from the Zoological Society of London. Despite its evolutionary and conservation relevance there remain important gaps in knowledge of the basic ecology of this species. Based on camera-trapping data, we estimated Baird´s tapir abundance and analyzed its patterns of daily activity and preference for different altitude intervals in El Triunfo Biosphere reserve, one of the last strongholds for this species in southern Mexico. We also applied a recently developed method (Random encounter model) to estimate tapir density without the need of individual identification. Tapir relative abundance was: 1.3 events/100 camera-trapdays and density: 0.12 ind./km2. Tapir activi...
Hispanics who speak Spanish are at risk for low health literacy. We evaluated Spanish language hy... more Hispanics who speak Spanish are at risk for low health literacy. We evaluated Spanish language hypertension (HTN) and diabetes mellitus (DM) patient education materials from U.S. federal agency public sector sources using the Suitability of Assessment (SAM) instrument. Mean readability for HTN materials was grade 7.9 and for DM materials was grade 6.6. Mean SAM score for HTN materials was 43.9 and for DM materials was 63.2. SAM scores were significantly better for DM than for HTN materials in overall score, content, graphics, layout, stimulation/motivation, and cultural appropriateness (p < .05). Clinicians should evaluate suitability of Spanish language HTN and DM materials that they use in patient teaching.
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