Optical Modulator with Linear Response

A purely linear resonant cavity interferometric modulator with a potential infinite spurious free dynamic range and multi-gigahertz bandwidth is described

Airway Epithelial Innate Immunity

Besides providing an essential protective barrier, airway epithelial cells directly sense pathogens and respond defensively. This is a frontline component of the innate immune system with specificity for different pathogen classes. It occurs in the context of numerous interactions with leukocytes, but here we focus on intrinsic epithelial mechanisms. Type 1 immune responses are directed primarily at intracellular pathogens, particularly viruses. Prominent stimuli include microbial nucleic acids and interferons released from neighboring epithelial cells. Epithelial responses revolve around changes in the expression of interferon-sensitive genes (ISGs) that interfere with viral replication, as well as the further induction of interferons that signal in autocrine and paracrine manners. Type 2 immune responses are directed primarily at helminths and fungi. Prominent pathogen stimuli include proteases and chitin, and important responses include mucin hypersecretion and chitinase release. Type 3 immune responses are directed primarily at extracellular microbial pathogens, including bacteria and fungi, as well as viruses during their extracellular phase of infection. Prominent microbial stimuli include bacterial wall components, such as lipopeptides and endotoxin, as well as microbial nucleic acids. Key responses are the release of reactive oxygen species (ROS) and antimicrobial peptides (AMPs). For all three types of response, paracrine signaling to neighboring epithelial cells induces resistance to infection over a wide field. Often, the epithelial effector molecules themselves also have signaling properties, in addition to the release of inflammatory cytokines that boost local innate immunity. Together, these epithelial mechanisms provide a powerful first line of pathogen defense, recruit leukocytes, and instruct adaptive immune responses

Characterizing Van Kampen Squares via Descent Data

Categories in which cocones satisfy certain exactness conditions w.r.t. pullbacks are subject to current research activities in theoretical computer science. Usually, exactness is expressed in terms of properties of the pullback functor associated with the cocone. Even in the case of non-exactness, researchers in model semantics and rewriting theory inquire an elementary characterization of the image of this functor. In this paper we will investigate this question in the special case where the cocone is a cospan, i.e. part of a Van Kampen square. The use of Descent Data as the dominant categorical tool yields two main results: A simple condition which characterizes the reachable part of the above mentioned functor in terms of liftings of involved equivalence relations and (as a consequence) a necessary and sufficient condition for a pushout to be a Van Kampen square formulated in a purely algebraic manner.Comment: In Proceedings ACCAT 2012, arXiv:1208.430

Social determinants of mental health in Italy: the role of education in the comparison of migrant and Italian residents

Mental health is impacted by social, economic, and environmental factors, the Social Determinants of Health (SDH). Migrants experiencing precarious living and working conditions may be more at risk of poor mental health than the majority population. This paper aims to evaluate the relationship of educational attainment and other SDH with depressive symptoms among the resident population, including Italians and migrants. This study examined the respondents to the Italian “Progressi delle Aziende Sanitarie per la Salute in Italia” (PASSI) surveillance system, 2014–18. The sample of 144.055 respondents is composed of the resident working adults aged 25–69 with Italian citizenship (n = 136.514) and foreign citizenship (n = 7.491). Findings show that among Italians high level of education appears to be a protective factor for mental health, in accordance with the international evidence (adjPR: tertiary education 0,74 p-value = 0.000). However, among immigrants high level of education is associated with the presence of depressive symptoms (adjPR: tertiary education: 1.61 p-value = 0.006), particularly for men (adjPR: tertiary education: 2.40 p-value = 0.006). The longer the length of stay in Italy for immigrants the higher the risk of depressive symptoms: adjPR for 10+ years: 2.23 p-value = 0.005. The data show that high education could represent a risk factor for mental health of immigrants. Moreover, among migrants there are some significant mental health inequities between male and female related to the duration of stay in Italy, economic activity and educational level. Considering that health is related to the nature of society as well as to access to technical solutions, multicultural societies require culturally oriented interventions for tackling health inequities. This means developing evidence-based policies in order to tackle health inequalities in the population as a whole, including culturally oriented measures in the larger framework of developing diversity sensitive services

Identification of novel host-oriented targets for Human Immunodeficiency Virus type 1 using Random Homozygous Gene Perturbation

<p>Abstract</p> <p>Background</p> <p>Human Immunodeficiency Virus (HIV) is a global threat to public health. Current therapies that directly target the virus often are rendered ineffective due to the emergence of drug-resistant viral variants. An emerging concept to combat drug resistance is the idea of targeting host mechanisms that are essential for the propagation of the virus, but have a minimal cellular effect.</p> <p>Results</p> <p>Herein, using Random Homozygous Gene Perturbation (RHGP), we have identified cellular targets that allow human MT4 cells to survive otherwise lethal infection by a wild type HIV-1_NL4-3. These gene targets were validated by the reversibility of the RHGP technology, which confirmed that the RHGP itself was responsible for the resistance to HIV-1 infection. We further confirmed by siRNA knockdowns that the RHGP-identified cellular pathways are responsible for resistance to infection by either CXCR4 or CCR5 tropic HIV-1 variants. We also demonstrated that cell clones with these gene targets disrupted by RHGP were not permissible to the replication of a drug resistant HIV-1 mutant.</p> <p>Conclusion</p> <p>These studies demonstrate the power of RHGP to identify novel host targets that are essential for the viral life cycle but which can be safely perturbed without overt cytotoxicity. These findings suggest opportunities for the future development of host-oriented therapeutics with the broad spectrum potential for safe and effective inhibition of HIV infection.</p

Serum SmD autoantibody proteomes are clonally restricted and share variable-region peptides

This article is under embargo for 12 months from the date of publication [Publication date: 7 Jan 2015] in accordance with publisher copyright policy.Recent advances in mass spectrometry-based proteomic methods have allowed variable (V)- region peptide signatures to be derived from human autoantibodies present in complex serum mixtures. Here, we analysed the clonality and V-region composition of immunoglobulin (Ig) proteomes specific for the immunodominant SmD protein subunit of the lupus-specific Sm autoantigen. Precipitating SmD-specific IgGs were eluted from native SmD-coated ELISA plates preincubated with sera from six patients with systemic lupus erythematosus (SLE) positive for anti-Sm/RNP. Heavy (H)- and light (L)-chain clonality and V-region sequences were analysed by 2-dimensional gel electrophoresis and combined de novo database mass spectrometric sequencing. SmD autoantibody proteomes from all six patients with SLE expressed IgG1 kappa restricted clonotypes specified by IGHV3-7 and IGHV1-69 H-chains and IGKV3-20 and IGKV2-28 L-chains, with shared and individual V-region amino acid replacement mutations. Clonotypic sharing and restricted V-region diversity of systemic autoimmunity can now be extended from the Ro/La cluster to Sm autoantigen and implies a common pathway of anti-Sm autoantibody production in unrelated patients with SLE

Effect of pioglitazone treatment on behavioral symptoms in autistic children

INTRODUCTION: Autism is complex neuro-developmental disorder which has a symptomatic diagnosis in patients characterized by disorders in language/communication, behavior, and social interactions. The exact causes for autism are largely unknown, but is has been speculated that immune and inflammatory responses, particularly those of Th2 type, may be involved. Thiazolidinediones (TZDs) are agonists of the peroxisome proliferator activated receptor gamma (PPARγ), a nuclear hormone receptor which modulates insulin sensitivity, and have been shown to induce apoptosis in activated T-lymphocytes and exert anti-inflammatory effects in glial cells. The TZD pioglitazone (Actos) is an FDA-approved PPARγ agonist used to treat type 2 diabetes, with a good safety profile, currently being tested in clinical trials of other neurological diseases including AD and MS. We therefore tested the safety and therapeutic potential of oral pioglitazone in a small cohort of children with diagnosed autism. CASE DESCRIPTION: The rationale and risks of taking pioglitazone were explained to the parents, consent was obtained, and treatment was initiated at either 30 or 60 mg per day p.o. A total of 25 children (average age 7.9 ± 0.7 year old) were enrolled. Safety was assessed by measurements of metabolic profiles and blood pressure; effects on behavioral symptoms were assessed by the Aberrant Behavior Checklist (ABC), which measures hyperactivity, inappropriate speech, irritability, lethargy, and stereotypy, done at baseline and after 3–4 months of treatment. DISCUSSION AND EVALUATION: In a small cohort of autistic children, daily treatment with 30 or 60 mg p.o. pioglitazone for 3–4 months induced apparent clinical improvement without adverse events. There were no adverse effects noted and behavioral measurements revealed a significant decrease in 4 out of 5 subcategories (irritability, lethargy, stereotypy, and hyperactivity). Improved behaviors were inversely correlated with patient age, indicating stronger effects on the younger patients. CONCLUSION: Pioglitazone should be considered for further testing of therapeutic potential in autistic patients