Study and Therapeutic Interference of T Cell Function in Pressure Overload-induced Heart Failure

Heart failure (HF) is a leading cause of mortality. Inflammation is implicated in HF, yet clinical trials targeting pro-inflammatory cytokines in HF were unsuccessful, possibly due to redundant functions of individual cytokines. We attempted to identify and exploit better targets in cardiac inflammation so as to enable an immunotherapy of HF. We linked T cells with HF development in the gold-standard mouse model of HF and in human HF patients. We inhibited T cell function in vivo via T cell costimulation blockade, through FDA-approved rheumatoid arthritis drug abatacept (CTLA-Ig). Administration of abatacept led to highly significant delay in progression and decreased severity of cardiac dysfunction in the mouse HF model. The therapeutic effect occurred via inhibition of activation and cardiac infiltration of T cells and macrophages, leading to reduced cardiomyocyte death. Treatment also induced production of anti-inflammatory cytokine interleukin-10 (IL-10). IL-10-deficient mice were refractive to treatment, whilst protection could be rescued by transfer of IL-10-sufficient B cells. These results suggest that T cell costimulation blockade could be therapeutically exploited as a possible HF treatment

ANALISA PENGARUH WAKTU PEMANFAATAN SOLAR CELL & LUAS HEADSINK TERHADAP SUHU

Kotak pendingin atau juga dikenal cooler box adalah tempat tempat untuk menyimpan es batu atau minuman dingin. Saat didalam rumah kita bisa memanfaatkan kulkas untuk menyimpan es batu atau minuman dingin. Namun saat kita beraktivitas diluar rumah sering kebingungan untuk menjaga es batu atau minuman dingin tersebut,maka dari itu cooler box hadir untuk menunjang aktivitas diluar rumah serta jauh dari sumber listrik. Disebabkan kotak pendingin berguna untuk menyimpan es atau minuman, banyak orang-orang menggunakan kotak tersebut untuk berbagai macam diantaranya untuk menyimpan daging,ikan,dan lain sebagainya.Tingkat kesegaran ikan akan semakin cepat menurun atau ikan akan mudah membusuk pada suhu tinggi namun sebaliknya jika suhu rendah dapat menghambat pembusukan. Maka dari pada itu banyak orang – orang berangsur menggunakan kotak pendingin untuk menyimpan ikan,karena didalam kotak pendingin dapat mengurangi bakteri pembusukan di suhu badan ikan. Dalam penelitian ini kami membuat kotak pendingin yang terbuat dari sytrofroam dengan bantuan alat seperti solar cell,battery,fan,heatsink,dan thermoelectric atau peltier.Kami menganalisa heatsink variable 8 x 10cm,9 x 10 cm, serta 10 x 12 cm selama 1 jam, 2 jam, serta 3 jam. Berdasarkan hasil yang  diperoleh  dari penelitian ini pada variable 8 x 10 cm dengan waktu 1 jam,dengan waktu tersebut menghasilkan  konveksi yang sama dengan radiasi.sehingga variable 8 x 10 lebih efektif dari pada variable yang lainnya. Kata kunci : Kotak Pendingin, head sink, solar cel

Analisis Kerusakan Turbin Angin Akibat Getaran Pada Pondasi

Turbin angin merupakan sebuah alat teknologi yang mengubah energi angin menjadi energi kinetik atau energi listrik.  Turbin angin sering mengalami kerusakan baik karena faktor angin maupun gempa bumi. Kerusakan turbin angin lebih sering terjadi adalah kerusakan pada pondasi. Kerusakan ini terjadi akibat adanya getaran pada pondasi turbin angin. Pada penelitian ini, turbin angin dipasang peredam pada pondasinya untuk mengurangi getaran yang terjadi pada pondasi sehingga meminimalisir kerusakan. Penelitian ini dilakukan dengan dua metode, yaitu simulasi dan eksperimen. Secara simulasi, analisis diakukan dengan menggunakan software. Secara eksperimen dilakukan dengan cara meletakkan turbin angin skala laboratorium di atas meja getar dimana nacelle, tiang, dan pondasi dianggap rigid. Kemudian dilakukan pengukuran menggunakan accelerometer yang dihubungkan pada Osciloscop. Accelerometer diletakkan tegak lurus pondasi. Selain itu, peredam diletakkan pada empat sisi pondasi. Peredam yang digunakan terbuat dari karet. Peredam ini mempunyai dua variasi bentuk, yaitu silinder dan runcing. Hasil penelitian secara simulasi dan eksperimen, kemampuan mereduksi getaran paling efektif ketika peredam dilettakkan pada posisi a= 12 cm dengan bentuk peredam silinder. Pada kondisi ini, peredam mampu menurunkan RMS respon percepaan dari 0,2969 m/s2  menjadi 0.1414 m/s2 untuk simulasi dan 0.5466 m/s2 menjadi 1.3572 m/s2 untuk eksperimen Kata kunci: Turbin Angin, Peredam, getara

Compartmentalisation of the immune response in human skin : cross-talk between dendritic cells and T cells in healthy conditions and in psoriasis

Human skin is highly compartmentalised and distinct subsets of dendritic cells (DCs) and T cells reside in epidermis and dermis. Alterations in the composition of DCs and T cells have been observed in psoriasis, a common cytokine-driven focal inflammatory skin disease. In this thesis we explore the functional profile of epidermal and dermal DCs and T cells in different phases of psoriasis, and how different cytokines present in homeostasis and inflammation affect the development of tissue resident memory T (Trm) cells. PAPER I: In lesional psoriasis, langerin- DCs accumulated in the epidermis. Both Langerhans cells (LCs) and epidermal DCs (eDCs) displayed upregulated pro-inflammatory genes and produced IL-23 after stimulation with ligands binding to toll-like receptor (TLR) 4 or 7/8. Elevated gene expression of IL23A and IL15 in LCs combined with their capacity to produce IL-23 upon TLR 7/8 stimulation suggested that LCs maintained their pro-inflammatory profile in resolved psoriasis. PAPER II: Granzymes (Gzms) and perforin are produced by cytotoxic T cells. Here we show that epidermal T cells produced GzmA in absence of perforin within psoriatic lesions. IL-17- stimulated human keratinocytes, in presence of GzmA, upregulated the production of CXCL1, CXCL12 and CCL4, involved in neutrophil and lymphocyte recruitment, therefore highlighting a new pathway of T cell driven recruitment of immune cells. PAPER III: In resolved psoriasis, epidermal resident T cells and LCs maintain a pronounced pro-inflammatory profile, whereas dermal T cells are less inflammatory. We observed an enrichment in the expression of the regulatory molecules FOXP3, CTLA4 and PD1 in T cells, and an increased IDO1 expression and IL-10 production by DCs. Clusters of Foxp3+ T cells and DCs were identified in the skin of UVB treated patients, hinting at a possible interaction between regulatory T cells and tolerogenic DCs in the dermis of resolved psoriatic lesions. PAPER IV: Healthy epidermis and dermis harbour phenotypically distinct subsets of Trm cells. Here we focused on the phenotypic and functional plasticity of skin CD8 Trm cells. Dermal Trm cells, mainly CD69+CD103-CD49a-, upregulated CD103 or both CD103 and CD49a after stimulation with TGF-b, IL-2 and IL-15. TCR engagement increased the proportion of CD103+CD49a+ cells. Conversely, epidermal Trm cells exposed to the same conditions did not change their phenotype, but their functional profile was affected by IL-17 polarising cytokines. Collectively, these studies highlight the high pro-inflammatory potential of epidermal DCs and T cells during different phases of psoriasis. In contrast, dermal cells acquire tolerogenic features in resolved disease. Moreover, we show that the functionality of Trm cells is affected by their surrounding milieu. These results encourage to take compartmental immune responses into consideration in the design of vaccines and targeted therapies

Trazodone treatment protects neuronal-like cells from inflammatory insult by inhibiting NF-κB, p38 and JNK

Growing evidence suggests that alterations of the inflammatory/immune system contribute to the pathogenesis of major depression and that inflammatory processes may influence the antidepressant treatment response. Depressed patients exhibit increased levels of inflammatory markers in both the periphery and brain, and high co-morbidity exists between depression and diseases associated with inflammatory alterations. Trazodone (TDZ) is a triazolopyridine derivative that belongs to the class of serotonin receptor antagonists and reuptake inhibitors. Although the trophic and protective properties of classic antidepressants have extensively been exploited, the effects of TDZ remain to be fully elucidated. In this study, the pharmacological activities of TDZ on human neuronal-like cells were investigated under both physiological and inflammatory conditions. An in vitro inflammatory model was established using lipopolysaccharide (LPS) and tumour necrosis factor-α (TNF-α), which efficiently mimic the stress-related changes in neurotrophic and pro-inflammatory genes.Our results showed that TDZ significantly increased the mRNA expression of both brain-derived nerve factor (BDNF) and cAMP response element-binding protein (CREB) and decreased the cellular release of the pro-inflammatory cytokine interferon gamma (IFN-γ) in neuronal-like cells.In contrast, neuronal cell treatment with LPS and TNF-α decreased the expression of CREB and BDNF and increased the expression of nuclear factor kappa B (NF-κB), a primary transcription factor that functions in inflammatory response initiation. Moreover, the two agents induced the release of pro-inflammatory cytokines (. i.e., interleukin-6 and IFN-γ) and decreased the production of the anti-inflammatory cytokine interleukin-10. TDZ pre-treatment completely reversed the decrease in cell viability and counteracted the decrease in BDNF and CREB expression mediated by LPS-TNF-α. In addition, the production of inflammatory mediators was inhibited, and the release of interleukin-10 was restored to control levels.Furthermore, the intracellular signalling mechanism regulating TDZ-elicited effects was specifically investigated. TDZ induced extracellular signal-regulated kinase (ERK) phosphorylation and inhibited constitutive p38 activation. Moreover, TDZ counteracted the activation of p38 and c-Jun NH2-terminal kinase (JNK) elicited by LPS-TNF-α, suggesting that the neuro-protective role of TDZ could be mediated by p38 and JNK.Overall, our results demonstrated that the protective effects of TDZ under inflammation in neuronal-like cells function by decreasing pro-inflammatory signalling and by enhancing anti-inflammatory signalling

Julolidine fluorescent molecular rotors as vapour sensing probes in polystyrene films

We introduce a new sensing polymer system for detection of volatile organic compounds (VOCs) based on the optical response of polystyrene (PS) films doped with julolidine fluorescent molecular rotors (FMRs). The julolidine FMRs exhibited viscosity-dependent changes in the fluorescence intensity, that was enhanced when glycerol was added to ethanol solutions and when they were dispersed in PS films. Thus, reduction in medium mobility slowed down internal motions and allowed for a major radiative decay pathway. The FMR/PS films were exposed to several VOCs, and showed a significant decrease in fluorescence emission when exposed to chloroform, whereas a negligible variation in their emission occurred when methanol was utilized. This vapour sensing behaviour was much more evident when a perfluorodecyl chain was linked to the julolidine core being the molecule segregated at the film surface. This responsive behaviour was affected by solvent composition and its reproducible response was easily determined by luminescence experiments

Aging, Cognitive Decline and Hearing Loss: Effects of Auditory Rehabilitation and Training with Hearing Aids and Cochlear Implants on Cognitive Function and Depression among Older Adults

A growing interest in cognitive effects associated with speech and hearing processes is spreading throughout the scientific community essentially guided by evidence that central and peripheral hearing loss is associated with cognitive decline. For the present research, 125 participants older than 65 years of age (105 with hearing impairment and 20 with normal hearing) were enrolled, divided into 6 groups according to their degree of hearing loss and assessed to determine the effects of the treatment applied. Patients in our research program routinely undergo an extensive audiological and cognitive evaluation protocol providing results from the Digit Span test, Stroop color-word test, Montreal Cognitive Assessment and Geriatric Depression Scale, before and after rehabilitation. Data analysis was performed for a cross-sectional and longitudinal study of the outcomes for the different treatment groups. Each group demonstrated improvement after auditory rehabilitation or training on shortand long-term memory tasks, level of depression and cognitive status scores. Auditory rehabilitation by cochlear implants or hearing aids is effective also among older adults (median age of 74 years) with different degrees of hearing loss, and enables positive improvements in terms of social isolation, depression and cognitive performance

Algunas direcciones de la literatura comparada en los comienzos del nuevo milenio

En las últimas décadas del Siglo XX, el impacto de los nuevos paradigmas epistemológicos y el surgimiento de nuevos campos disciplinares y teorías literarias produjeron la desestructuración de los sistemas jerárquicos que en la teoría y práctica de la literatura comparada habían privilegiado la producción literaria de las culturas centrales. El nuevo comparatismo fue entendido entonces como diálogo de culturas y factor de conocimiento y convivialidad. Entrado el Siglo XXI, quiero detenerme en tres direcciones del comparatismo. Una que apunta a la profundización del enfoque interdisciplinario, una segunda que muestra un renovado retorno a la crítica temática para explorar comparativamente la construcción dialógica de conceptos centrales en el marco de una globalización hegemónica y también contrahegemónica, y, por último, una aproximación a los relatos de sujetos migrantes/cosmopolitas que desafían los criterios geopolíticos, culturales y hasta lingüísticos para definir las identidades literarias. Como ejemplo de la primera tendencia, haré referencia a estudios en literatura comparada sobre la conexión de la literatura con las ciencias duras. Ejemplificaré la segunda dirección -instancia también del énfasis actual en lo multidisciplinario- con un estudio de casos a propósito de la construcción dialógica del concepto de justicia en el discurso social y en las artes contemporáneas. Finalmente, con respecto a los relatos de sujetos migrantes, me detendré en la obra Incendies (2003) de Wajdi Mouawad y en beatrice & virgil (2010) de Yann Martel, ambos residentes actualmente en Canadá.Panel de comparatismoCentro de Estudios de Teoría y Crítica Literari

Anisotropy and NMR spectroscopy

Abstract In this paper, different aspects concerning anisotropy in Nuclear Magnetic Resonance (NMR) spectroscopy have been reviewed. In particular, the relevant theory has been presented, showing how anisotropy stems from the dependence of internal nuclear spin interactions on the molecular orientation with respect to the external magnetic field direction. The consequences of anisotropy in the use of NMR spectroscopy have been critically discussed: on one side, the availability of very detailed structural and dynamic information, and on the other side, the loss of spectral resolution. The experiments used to measure the anisotropic properties in solid and soft materials, where, in contrast to liquids, such properties are not averaged out by the molecular tumbling, have been described. Such experiments can be based either on static low-resolution techniques or on one- and two-dimensional pulse sequences exploiting Magic Angle Spinning (MAS). Examples of applications of NMR spectroscopy have been shown, which exploit anisotropy to obtain important physico-chemical information on several categories of systems, including pharmaceuticals, inorganic materials, polymers, liquid crystals, and self-assembling amphiphiles in water. Solid-state NMR spectroscopy can be considered, nowadays, one of the most powerful characterization techniques for all kinds of solid, either amorphous or crystalline, and semi-solid systems for the obtainment of both structural and dynamic properties on a molecular and supra-molecular scale. Graphic abstrac

Enhancement of Zn tolerance and accumulation in plants mediated by the expression of Saccharomyces cerevisiae vacuolar transporter ZRC1

Main conclusion Transgenic Arabidopsis thaliana and Populus alba plants overexpressing the zinc transporter ScZRC1 in shoots exhibit Zn tolerance. Increased Zn concentrations were observed in shoots of P. alba, a species suitable for phytoremediation. Genetic engineering of plants for phytoremediation is worth to consider if genes leading to heavy metal accumulation and tolerance are expressed in high biomass producing plants. The Saccharomyces cerevisiae ZRC1 gene encodes a zinc transporter which is primarily involved in the uptake of Zn into the vacuole. The ZRC1 gene was expressed in the model species A. thaliana and P. alba (cv. Villafranca). Both species were transformed with constructs carrying ScZRC1 under the control of either the CaMV35S promoter for constitutive expression or the active promoter region of the tobacco Rubisco small subunit (pRbcS) to limit the expression to the above-ground tissues. In hydroponic cultures, A. thaliana and poplar ScZRC1-expressing plants accumulated more Zn in vegetative tissues and were more tolerant than untransformed plants. No differences were found between plants carrying the CaMV35::ScZRC1 or pRbcS::ScZRC1 constructs. The higher Zn accumulation in transgenic plants was accompanied by an increased superoxide dismutase (SOD) activity, indicating the activation of defense mechanisms to prevent cellular damage. In the presence of cadmium in addition to Zn, plants did not show symptoms of metal toxicity, neither in hydroponic cultures nor in soil. Zn accumulation increased in shoots, while no differences were observed for Cd accumulation, in comparison to control plants. These data suggest that ectopic expression of ScZRC1 can increase the potential of poplar for the remediation of Zn-polluted soils, although further tests are required to assay its application in remediating multimetal polluted soils