Host-Commensal Cross Talk at the Cutaneous interface

Our body\u27s epithelial surfaces are colonized by a diverse array of commensal organisms. While the contribution of intestinal commensals to metabolism, tissue development, and immunity has been extensively examined, the role of flora inhabiting other barrier sites in maintaining host physiology is poorly understood. Moreover, how resident commensals control unique physiological niches and the mechanisms underlying the host-microbial dialogue in distinct tissue sites requires elucidation. In Chapter 2 we find that murine skin, similar to human skin, houses unique commensal communities in topologically distinct niches. Furthermore, skin sites of both mice and non-human primates enriched with commensal niches contain more inflammatory T cells. Given that the skin forms a critical interface with the terrestrial environment and is an opportunistic site for pathogen entry, this tissue represents a highly relevant barrier site for studying the discrete interactions between resident immune cells and local flora outside the intestine. The findings presented in Chapter 3 support a non-redundant role for the resident skin microbiota in setting the cutaneous inflammatory tone. More specifically, germ-free mice have an imbalance of effector and regulatory T cells in the skin that can be reversed upon addition of skin, but not gut, flora. Additionally, skin commensals act as natural adjuvants, boosting both protective immunity and pathology during Leishmania major infection. Thus, signals from the indigenous microbiota are necessary for optimal tissue immune fitness and function in the skin under steady state conditions and during infectious challenge. In Chapter 4, we identify the interleukin-1 receptor (IL-1R1) as an essential regulator of cutaneous T cell function. Accordingly, mice deficient in IL-1R1 and its downstream signaling adaptor, Myd88, recapitulate the homeostatic and immune defects observed in the skin of germ-free mice. Emphasizing the partitioning of innate signals in the skin and gut, IL-1 signaling is dispensable for intestinal T cell function. Importantly, cutaneous commensals locally amplify IL-1/MyD88, signaling to tune the function of effector T cells in the dermis. Taken together, these studies underscore the importance of the microbiota as a distinctive feature of tissue compartmentalization and provide insight into the mechanisms of immune regulation by resident commensal niches in health and disease

Implementing and Characterizing Real-time Broadband RFI Excision for the GMRT Wideband Backend

The Giant Metrewave Radio Telescope (GMRT) is being upgraded to increase the receiver sensitivity. This makes the receiver more susceptible to man-made Radio Frequency Interference (RFI). To improve the receiver performance in presence of RFI, real-time RFI excision (filtering) is incorporated in the GMRT wideband backend (GWB). The RFI filtering system is implemented on FPGA and CPU-GPU platforms to detect and remove broadband and narrowband RFI. The RFI is detected using a threshold-based technique where the threshold is computed using Median Absolute Deviation (MAD) estimator. The filtering is carried out by replacing the RFI samples by either noise samples or constant value or threshold. This paper describes the status of the real-time broadband RFI excision system in the wideband receiver chain of the upgraded GMRT (uGMRT). The test methodology for carrying out various tests to demonstrate the performance of broadband RFI excision at the system level and on radio astronomical imaging experiments are also described.Comment: 7 pages, 7 figure

Leadership Styles in India- An empirical Study of Indian Entrepreneurs/Leaders

The word Leader simply means a person who leads. A leader should necessarily possess the characteristics of organizing, staffing, training, motivating, recognizing the special capabilities and talents, setting standards, correcting deviations, achieving objectives etc. or by guiding his subordinates and showing the way to be followed in order to reach the organizational goal. Each and every person has to either lead or follow. This is decided on the basis of aptitude, potential and determination.Very few are daring and courageous enough to risk unpopularity by depending from the herd. The ability to make a spot decision is what differentiates the executive or leader from the clerk. A leader always exerts a positive influence on the life of others, as a member of team or the head of a small department. The role of an effective leader is value addition. Leadership is a multi-dimensional, multi-faceted, multi-situational and multi-role concept."Management is doing things right; leadership is doing the right things." There are nine key qualities that research shows people seek in a successful leader:Passion; Decisiveness; Conviction; Integrity; Adaptability; Emotional Toughness; Emotional Resonance; Self Knowledge; Humility This study intends to study various approaches to leadership adopted by entrepreneurs and leaders in India, specifically those in cities selected for the study. Effectively, the data were analysed and conclusions were drawn

The microbiome in patients with atopic dermatitis.

As an interface with the environment, the skin is a complex ecosystem colonized by many microorganisms that coexist in an established balance. The cutaneous microbiome inhibits colonization with pathogens, such as Staphylococcus aureus, and is a crucial component for function of the epidermal barrier. Moreover, crosstalk between commensals and the immune system is now recognized because microorganisms can modulate both innate and adaptive immune responses. Host-commensal interactions also have an effect on the developing immune system in infants and, subsequently, the occurrence of diseases, such as asthma and atopic dermatitis (AD). Later in life, the cutaneous microbiome contributes to the development and course of skin disease. Accordingly, in patients with AD, a decrease in microbiome diversity correlates with disease severity and increased colonization with pathogenic bacteria, such as S aureus. Early clinical studies suggest that topical application of commensal organisms (eg, Staphylococcus hominis or Roseomonas mucosa) reduces AD severity, which supports an important role for commensals in decreasing S aureus colonization in patients with AD. Advancing knowledge of the cutaneous microbiome and its function in modulating the course of skin disorders, such as AD, might result in novel therapeutic strategies

La croissance d'un cerveau bruyant : développement de la variabilité structurée des réponses neuronales et ses implications

Les nourrissons apprennent des représentations précises des stimuli malgré des délais plus longs dans la transmission de l'information et une architecture anatomique et fonctionnelle qui évolue rapidement à cet âge. Malgré de nombreuses recherches sur le traitement des stimuli sensoriels, les mécanismes computationnels de base qui sous-tendent cet apprentissage restent flous. Ce manque de compréhension adéquate peut être lié à la dynamique cérébrale, qui est essentielle au fonctionnement du cerveau, a été peu étudiée. Cette thèse donc se concentre sur la variabilité de l'activité neuronale. Dans la première étude, je fournis des preuves empiriques de l'existence et du développement de modulations structurées et pertinentes au stimulus de la variabilité neuronale chez les nourrissons et je montre que la structure temporelle des modulations faibles de la variabilité dépend de la difficulté de la tâche à accomplir. L'interprétation des systèmes dynamiques de ces résultats nous permet de suggérer que les composantes des potentiels évoqués (CEP) agissent comme des modes faiblement attractifs dans lesquels les trajectoires neuronales sont temporairement contraintes par l'arrivée du stimulus. Dans la seconde étude, à l'aide d'un modèle simple qui approxime l'activité du champ moyen des populations excitatrices et inhibitrices (E-I) au sein d'un circuit cortical, nous relions la maturation des conductances E-I à la quantité de jitter, fournissant une explication possible à la maturation observée de la variabilité des réponses au cours du développement précoce. Cette thèse plaide donc en faveur de l'étude des statistiques de second ordre souvent considérées comme du bruit.Infants learn accurate stimulus representations in the face of substantially longer information transmission delays, and quickly changing anatomical and functional architecture at this age. Despite a large amount of research examining how the processing of sensory stimuli becomes progressively structured throughout early development, the basic computational mechanisms underpinning such a learning feat remain unclear. This lack of adequate understanding could be due to the fact that some aspects of brain dynamics, which are critical to brain function, have been understudied. To close this gap,this thesis will focus on the variability of neural activity. In the first study, I provide empirical evidence for the existence and development of structured, stimulus-relevant modulations of neural variability in infants and in adults and show that the temporal structure of weak variability modulations depend on the difficulty of the task at hand. Dynamical systems interpretation of these results allows us to suggest that the Event-Related Potential (ERP) components act as weakly attracting modes of a low-dimensional energy landscape in which neural trajectories are transiently constrained due to stimulus arrival. In the second study, using a simple computational model that approximates mean-field activity of excitatory and inhibitory (E-I) populations within a generic local cortical circuit, we relate maturation in E-I conductances to the amount of jitter, and thus provides a possible explanation for the observed maturation of response variability during early development. This thesis hence advocates for studying the second-order statistics often discarded as noise

Experiences of Dispute Resolution in Non-Court Forums: Justice Sans Rule Of Law?

Dispute resolution in India involves several actors and institutions – not only courts but also various other forums for alternative means of dispute resolution. While the judiciary is the sole authority responsible for redressing rights’ violations, the problems plaguing the judicial system contribute significantly to parties opting to settle disputes out of court. In this paper, we examine the functioning of some non-court forums, with a special focus on the question of women’s rights, autonomy, and agency in dispute resolution processes. We ask whether the working of such non-court forums is in consonance with the values of the Indian Constitution, especially the rule of law. In the context of women’s rights, we ask whether these forums take a legally neutral or gendered approach, and whether they speak they give primacy to rights or prioritise community and conciliation. To find answers, we analyse data from surveys and interviews undertaken by DAKSH to review the attitudes and approaches of such noncourt forums. We argue that valorising non-court forums as ‘quick, flexible, and effective’ while disregarding their subjectivity, arbitrariness, and lack of accountability – both to the individuals who approach them and to the society in which they function – amounts to a betrayal of constitutional values. We also argue that while all citizens, women included, must have the autonomy to choose any forum to resolve their disputes, that choice must not be governed by tradition, nor be influenced by lack of awareness of rights, or worse, failure of the state in ensuring speedy and effective dispute resolution

Repairing artifacts in neural activity recordings using low-rank Matrix estimation

International audienceElectrophysiology recordings are frequently affected by artifacts (e.g., subject motion or eye movements), which reduces the number of available trials and affects the statistical power. When artifacts are unavoidable and data are scarce, signal reconstruction algorithms that allow for the retention of sufficient trials become crucial. Here, we present one such algorithm that makes use of large spatiotemporal correlations in neural signals and solves the low-rank matrix completion problem, to fix artifactual entries. The method uses a gradient descent algorithm in lower dimensions to learn the missing entries and provide faithful reconstruction of signals. We carried out numerical simulations to benchmark the method and estimate optimal hyperparameters for actual EEG data. The fidelity of reconstruction was assessed by detecting event-related potentials (ERP) from a highly artifacted EEG time series from human infants. The proposed method significantly improved the standardized error of the mean in ERP group analysis and a between-trial variability analysis compared to a state-of-the-art interpolation technique. This improvement increased the statistical power and revealed significant effects that would have been deemed insignificant without reconstruction. The method can be applied to any time-continuous neural signal where artifacts are sparse and spread out across epochs and channels, increasing data retention and statistical power

Immune-Epithelial Cross Talk in Regeneration and Repair

International audienceThe epithelial tissues that line our body, such as the skin and gut, have remarkable regenerative prowess and continually renew throughout our lifetimes. Owing to their barrier function, these tissues have also evolved sophisticated repair mechanisms to swiftly heal and limit the penetration of harmful agents following injury. Researchers now appreciate that epithelial regeneration and repair are not autonomous processes but rely on a dynamic cross talk with immunity. A wealth of clinical and experimental data point to the functional coupling of reparative and inflammatory responses as two sides of the same coin. Here we bring to the fore the immunological signals that underlie homeostatic epithelial regeneration and restitution following damage. We review our current understanding of how immune cells contribute to distinct phases of repair. When unchecked, immune-mediated repair programs are co-opted to fuel epithelial pathologies such as cancer, psoriasis, and inflammatory bowel diseases. Thus, understanding the reparative functions of immunity may advance therapeutic innovation in regenerative medicine and epithelial inflammatory diseases

Mathematical modeling deciphering balance between cell survival and cell death using insulin

When modelling cell signalling networks, a balance must be struck between mechanistic detail and ease of interpretation. In this paper we apply a deterministic numerical method to the analysis of a large, systematic dataset describing the dynamics of cell signalling downstream of, tumor necrosis factor-a (TNF), epidermal growth factor (EGF), and insulin receptors in human colon carcinoma cells. Deterministic modeling is useful as a means to assemble and test what we know about proteins and networks. We extensively study the space of parameters to show that the model is structurally stable and robust over a broad range of parameter values. We have made the biological view of the main paths of the insulin input showing cell survival and cell death. Than with the help of different parameters relating to that protein present in the model we have designed scheme of the biochemical paths/deterministic model. With those parameters equations were formed which vary with time i.e. differential equation. Thus, our model is suitable for implementation in multi-scale simulation programs that are presently under development to study the behavior of large tumor cell populations

Evaluation of three different agents for in-office treatment of dentinal hypersensitivity: A controlled clinical study

Context: Dentin desensitizers are used for in-office treatment of dentinal hypersensitivity. They block the open tubules and bring about a reduction in hypersensitivity. Aim: The aim was to evaluate and compare the clinical effectiveness of a dentin desensitizer, a combination of a dentin desensitizer + adhesive and one-bottle self-etching adhesive for in-office treatment of dentin hypersensitivity. Settings and Design: Institutional, prospective double-blind parallel clinical design. Subjects and Methods: A total of 54 teeth in 20 patients were randomly allocated to one of the three study groups, with 18 teeth in each group as follows: Group A-Gluma Desensitizer (GD), Group B-Gluma Comfort Bond + Desensitizer (GCBD), Group C-Single Bond Universal (SBU). The patients′ dentinal hypersensitivity scores for tactile (hand-held scratch device), thermal (cold), and evaporative (dental unit air syringe) stimuli were recorded on a visual analog scale. The parameters were recorded at baseline, immediately after application of the agent, 3- and 6-week posttreatment. Statistical Analysis Used: The data were analyzed with Friedman′s test, Wilcoxon signed ranks test, Kruskal-Wallis test, and Mann-Whitney-U-test (P < 0.05). Results: All three groups showed a significant reduction in dentinal hypersensitivity (P < 0.05) compared to baseline at all time intervals. Statistically, significant differences were noted between GD and SBU; between GCBD and SBU in all testing parameters. Between GD and GCBD no significant difference was noted. Conclusions: GD and GCBD showed a greater reduction in dentin hypersensitivity than SB