Fully reconfigurable Mach Zehnder interferometers for the storage of photonic entanglement in a laser written photonic chip

LAUREA MAGISTRALELe memorie quantistiche sono un’importante stromento per la fotonica quantistica, poichè permettono di sincronizzare dispositivi diversi in cui avvengono processi probabilistici. La realizzazione di memorie quantistiche efficienti e con lunghi tempi di coerenza è di primaria importanza per molte applicazioni, tra cui la creazione di network quantistici sicuri su larga scala. Questa tesi è mirata alla realizzazione di una coppia di circuiti fotonici integrati contentnti interferometri Mach Zehnder riconfigurabili, da usare assieme a una coppia di memorie quantistiche a stato solido per l’immagazzinamento entanglement fotonico. Gli interferometri sono fabbricati tramite scrittura laser a femtosecondi in chip di vetro borosilicato. Un interferometro verrà posizionato prima delle memorie quantistiche per la preparazione dello stato da immagazzinare, mentre l’altro seguirà le memorie per condurre una tomografia sullo stato in uscita da esse. Ogni interferometro è dotato di due microriscaldatori per il controllo delle fasi interne ed esterne tramite effetto termo-ottico. Per rendere più efficiente la dissipazione di calore, sono state realizzate microstrutture di isolamento sotto ai microriscaldatori. I dispositivi sono stati ottimizzati per lavorare a 607 nm, così da essere usati assieme alle memorie quantistiche, già disponibili. Le strutture guidanti mostrano perdite di propagazione fino a 0.13 dB/cm e buon mode-matching con fibre ottiche a singolo modo in commercio. Il dispositivo globale può essere usato per l’immagazzinamento di qubit fotonici pathencoded secondo lo schema AFC - atomic frequency comb.Quantum memories are important tools in quantum photonics, in which they allow the syncrhronization of multiple devices when many different probabilistic quantum processes are linked together. The realization of efficient, long-lived quantum memories is of paramount importance for many applications, for example the creation of large scale secure quantum networks. This thesis work aimes the realization of a pair of integrated photonic waveguide circuits containing reconfigurable Mach Zehnder interferometers compatible with solid state quantum memories for the construction of a hybrid glass-crystal integrated platform capable of storing photonic entanglement. The interferometers are fabricated by femtosecond laser micromachining in borosilicate glass. One interferometer will be placed before the quantum memories to create the path entanglement, while the other will be placed after the memories and it will allow to carry out tomography of the output state. Each interferometer is equipped with two microheaters patterned on top of it, to allow for the control of the internal and external phases exploiting the thermo-optic effect. Isolation microstructures are realized by laser ablation beneath each microheater to improve the heating efficiency. The devices have been optimized to work at a wavelength of 607 nm to be used together with the already available quantum memories. Propagation losses as low as 0.13 dB/cm are obtained for the optical waveguides, together with good mode matching with commercial single-mode fibers. The final device can be used to store path-encoded photonic qubits following the Atomic Frequency Comb protocol for operating the quantum memory

Stem cell therapy for the treatment of early stage avascular necrosis of the femoral head: a systematic review

BACKGROUND: Avascular necrosis (AVN) of the femoral head (FH) is believed to be caused by a multitude of etiologic factors and is associated with significant morbidity in younger populations. Eventually, the disease progresses and results in FH collapse. Thus, a focus on early disease management aimed at joint preservation by preventing or delaying progression is key. The use of stem cells (SC) for the treatment of AVN of the FH has been proposed. We undertook a systematic review of the medical literature examining the use of SC for the treatment of early stage (precollapse) AVN of the FH, in both pre-clinical and clinical studies. METHODS: Data collected included: Pre-clinical studies – model of AVN, variety and dosage of SC, histologic and imaging analyses. Clinical studies – study design, classification and etiology of AVN, SC dosage and treatment protocol, incidence of disease progression, patient reported outcomes, volume of necrotic lesion and hip survivorship. RESULTS: In pre-clinical studies, the use of SC uniformly demonstrated improvements in osteogenesis and angiogenesis, yet source of implanted SC was variable. In clinical studies, groups treated with SC showed significant improvements in patient reported outcomes; however hip survivorship was not affected. Discrepancies regarding dose of SC, AVN etiology and disease severity were present. CONCLUSIONS: Routine use of this treatment method will first require further research into dose and quality optimization as well as confirmed improvements in hip survivorship

High-Resolution Genetics Identifies the Lipid Transfer Protein Sec14p as Target for Antifungal Ergolines.

Invasive infections by fungal pathogens cause more deaths than malaria worldwide. We found the ergoline compound NGx04 in an antifungal screen, with selectivity over mammalian cells. High-resolution chemogenomics identified the lipid transfer protein Sec14p as the target of NGx04 and compound-resistant mutations in Sec14p define compound-target interactions in the substrate binding pocket of the protein. Beyond its essential lipid transfer function in a variety of pathogenic fungi, Sec14p is also involved in secretion of virulence determinants essential for the pathogenicity of fungi such as Cryptococcus neoformans, making Sec14p an attractive antifungal target. Consistent with this dual function, we demonstrate that NGx04 inhibits the growth of two clinical isolates of C. neoformans and that NGx04-related compounds have equal and even higher potency against C. neoformans. Furthermore NGx04 analogues showed fungicidal activity against a fluconazole resistant C. neoformans strain. In summary, we present genetic evidence that NGx04 inhibits fungal Sec14p and initial data supporting NGx04 as a novel antifungal starting point

TLR3 essentially promotes protective class I–restricted memory CD8+ T-cell responses to Aspergillus fumigatus in hematopoietic transplanted patients

Aspergillus fumigatus is a model fungal pathogen and a common cause of severe infections and diseases. CD8+ T cells are present in the human and murine T-cell repertoire to the fungus. However, CD8+ T-cell function in infection and the molecular mechanisms that control their priming and differentiation into effector and memory cells in vivo remain elusive. In the present study, we report that both CD4+ and CD8+ T cells mediate protective memory responses to the fungus contingent on the nature of the fungal vaccine. Mechanistically, class I MHC-restricted, CD8+ memory T cells were activated through TLR3 sensing of fungal RNA by cross-presenting dendritic cells. Genetic deficiency of TLR3 was associated with susceptibility to aspergillosis and concomitant failure to activate memory-protective CD8+ T cells both in mice and in patients receiving stem-cell transplantations. Therefore, TLR3 essentially promotes antifungal memory CD8+ T-cell responses and its deficiency is a novel susceptibility factor for aspergillosis in high-risk patients.These studies were supported by the Specific Targeted Research Project ALLFUN (FP7-HEALTH-2009 contract number 260338 to L.R.), by SYBARIS (FP7-HEALTH-2009 contract number 242220 to L.R.), and by the Italian Project AIDS 2010 by the Istituto Superiore di Sanita (contract number 40H40 to L.R.). A.C. and C.C. were supported by fellowships from Fundacao para a Ciencia e Tecnologia, Portugal (contracts SFRH/BPD/46292/2008 and SFRH/BD/65962/2009, respectively)

Comorbidity as a driver of adverse outcomes in people with chronic kidney disease

Chronic kidney disease (CKD) is associated with poor outcomes, perhaps due to a high burden of comorbidity. Most studies of CKD populations focus on concordant comorbidities, which cause CKD (such as hypertension and diabetes) or often accompany CKD (such as heart failure or coronary disease). Less is known about the burden of mental health conditions and discordant conditions (those not concordant but still clinically relevant, like dementia or cancer). Here we did a retrospective population-based cohort study of 530,771 adults with CKD residing in Alberta, Canada between 2003 and 2011. Validated algorithms were applied to data from the provincial health ministry to assess the presence/absence of 29 chronic comorbidities. Linkage between comorbidity burden and adverse clinical outcomes (mortality, hospitalization or myocardial infarction) was examined over median follow-up of 48 months. Comorbidities were classified into three categories: concordant, mental health/chronic pain, and discordant. The median number of comorbidities was 1 (range 0-15) but a substantial proportion of participants had 3 and more, or 5 and more comorbidities (25 and 7%, respectively). Concordant comorbidities were associated with excess risk of hospitalization, but so were discordant comorbidities and mental health conditions. Thus, discordant comorbidities and mental health conditions as well as concordant comorbidities are important independent drivers of the adverse outcomes associated with CKD.</p

Estudo Histopatológico e Viabilidade de Análises do DNA em Ossadas Humanas Expostas a Condições Tafonômicas: aplicações na identificação forense

BV UNIFESP: Teses e dissertaçõe

Eosinophils Are Recruited in Response to Chitin Exposure and Enhance Th2-Mediated Immune Pathology in Aspergillus fumigatus Infection

In patients infected with the fungus Aspergillus fumigatus, Th1 responses are considered protective, while Th2 responses are associated with increased morbidity and mortality. How host-pathogen interactions influence the development of these protective or detrimental immune responses is not clear. We compared lung immune responses to conidia from two fungal isolates that expressed different levels of the fungal cell wall component chitin. We observed that repeated aspirations of the high-chitin-expressing isolate Af5517 induced increased airway eosinophilia in the lungs of recipient mice compared to the level of eosinophilia induced by isolate Af293. CD4+ T cells in the bronchoalveolar lavage fluid (BALF) of Af5517-aspirated mice displayed decreased gamma interferon secretion and increased interleukin-4 transcription. In addition, repeated aspirations of Af5517 induced lung transcription of the Th2-associated chemokines CCL11 (eotaxin-1) and CCL22 (macrophage-derived chemokine). Eosinophil recruitment in response to conidial aspiration was correlated with the level of chitin exposure during germination and was decreased by constitutive lung chitinase expression. Moreover, eosinophil-deficient mice subjected to multiple aspirations of Af5517 prior to neutrophil depletion and infection exhibited decreased morbidity and fungal burden compared to the levels of morbidity and fungal burden found in wild-type mice. These results suggest that exposure of chitin in germinating conidia promotes eosinophil recruitment and ultimately induces Th2-skewed immune responses after repeated aspiration. Furthermore, our results suggest that eosinophils should be examined as a potential therapeutic target in patients that mount poorly protective Th2 responses to A. fumigatus infection

Using Mutli Criteria Decision Analysis To Develop Sustainability Assessment Tools: Biomass Supply Chains

Energy access remains a significant challenge in nations lacking access to resources and strong infrastructure systems, creating barriers to economic development and to increased standards of living. Small scale biomass gasification energy (BGE) systems have been developed to meet energy needs in rural areas, creating synergies between agricultural and agro-forestry systems through utilization of biomass feedstock for energy generation. The sustainability of such systems requires sophisticated planning and coordination of the biomass supply chain. The goal of this thesis is to investigate and improve structural and process related characteristics of sustainability assessments for small scale bio-energy systems, specifically focusing on establishment and management of biomass supply chains through the development and dissemination of a generic sustainability assessment framework for biomass supply chains of small-scale BGE systems in rural East Africa. Building on a preliminary sustainability assessment framework (Christensen, 2013; Joerg, 2013) this research develops an assessment tool designed to capture sustainability requirements of the biomass supply chain in the ecological, social, and economic spheres through testing on three case studies in rural Uganda. Application and analysis of a preliminary framework on pilot projects in a rural east African context using Multi Criteria Decision Analysis (MCDA) methodologies contributes to development of strategies for energy system analysis and building stakeholder capacity to incorporate social, economic, and environmental considerations. The assessment process is outlined, including scoring, data collection, contextual considerations. Model application is discussed, including the impact of weighting on decision outcomes, uncertainty management, sensitivity analysis, and identification of tradeoffs among criteria. Finally, discussion of tool usefulness verses usability contributes to bridging academic research with practitioner priorities

Predictors of persistent medically unexplained physical symptoms: findings from a general population study

Objective: To explore the course persistency of Medically Unexplained Symptoms (MUS) and its prognostics factors in the general adult population. Knowledge of prognostic factors of MUS may indicate possible avenues for intervention development. Methods: Data were derived from the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2), a nationally representative face-to-face cohort study among the Dutch general population aged 18-64 years. We selected subjects with MUS at baseline and who participated at follow-up (N=324) and reassessed those subjects for having MUS at three year follow-up. Logistic regression analyses were used to determine risk factors for persistency of MUS. Results: 36.4% of the subjects had persistent MUS at follow-up. In logistic regression analyses adjusted for sex and age, persistency of MUS was predicted by the number of comorbid chronic medical disorder(s), lower education, female sex, not having a paid job, parental psychopathology as well as lower functioning. In the logistic regression analysis in which all significant variables adjusted for sex and age were entered simultaneously, three variables predicted persistent MUS: parental psychopathology, the number of comorbid chronic medical disorder(s) and physical functioning, with odds ratios of 2.01 (1.20-3.38), 1.19 (1.01-1.40) and 0.99 (0.97-1.00), respectively. Conclusion: In the adult general population, MUS were persistent in over one third of the subjects with MUS at baseline. Persistency was uniquely significantly predicted by parental psychopathology, number of comorbid chronic medical disorders and physical functioning. These findings warrant further research into early intervention and treatment options for persons with an increased risk of persistent MUS