Operational experiences of a TDHP system for solar cooling and heating of a canteen

Part of: Thermally driven heat pumps for heating and cooling. – Ed.: Annett Kühn – Berlin: Universitätsverlag der TU Berlin, 2013 ISBN 978-3-7983-2686-6 (print) ISBN 978-3-7983-2596-8 (online) urn:nbn:de:kobv:83-opus4-39458 [http://nbn-resolving.de/urn:nbn:de:kobv:83-opus4-39458]Solar cooling systems offer the possibility to use primarily the renewable energy source solar heat for space cooling. Moreover, a solar cooling system can also be used to provide heat for space heating, in the case of working in heat pump mode. Besides theoretical investigations practical experience is required to evaluate the performance of solar cooling in the field. This document presents the main results from a solar cooling installation for canteen cooling, which is in operation since 2007. The data evaluation shows a seasonal electrical performance factor of 26.1 for space heating and 6.5 for space cooling. A seasonal thermal performance factor for cooling of 0.4 has been determined

Fingolimod for Multiple Sclerosis: Mechanism of Action, Clinical Outcomes, and Future Directions

The oral sphingosine 1-phosphate receptor (S1PR) modulator fingolimod functionally antagonizes S1PR hereby blocking lymphocyte egress from secondary lymphoid organs to the peripheral blood circulation. This results in a reduction in peripheral lymphocyte counts, including potentially encephalitogenic T cells. In patients with relapsing multiple sclerosis fingolimod has been shown to be an effective treatment. In phase 2 and phase 3 studies fingolimod-treated patients had reduced disease activity clinically and in MRI. Although severe infectious complications occurred in single cases treated with fingolimod, the frequency of overall infections was comparable in fingolimod-treated patients and controls. Overall, in clinical studies fingolimod was well tolerated and had a favorable safety profile. In follow-up studies with continuous fingolimod, treatment showed sustained efficacy while being well tolerate

Hodgkin's Lymphoma and Paraneoplastic Phenomena in the Central Nervous System: A Case Report and Review of the Literature

A 25-year-old male patient presented to our Ear, Nose and Throat clinic with a history of nausea, vomiting, headache, vertigo and weight loss of 5 kg over the preceding 3 months. An enlarged cervical lymph node was detected at clinical examination. Lymph node biopsy showed nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL, nodular paragranuloma). Because of the neurological symptoms a cerebral MRI scan was performed and revealed an intense perivascular, bilateral, contrast-medium enhancing lesion of the temporal lobes suggestive of cerebral vasculitis. Cerebrospinal fluid analysis showed an increased number of mononuclear cells, but there was no indication for neurotropic viral or bacterial infections. EEG revealed a left temporal epileptic focus, and anti-epileptic therapy was initiated. NLPHL was treated with 2 cycles of ABVD chemotherapy and 20 Gy involved-field radiotherapy. Steroid therapy (prednisone 100 mg q.d.) for the presumed paraneoplastic neurological manifestation was started 1 week before chemotherapy and led to the rapid disappearance of complaints. Because of renewed onset of nausea and vertigo after 3 weeks of treatment with ABVD chemotherapy and 4 weeks of treatment with steroids, a follow-up brain MRI and EEG were performed and demonstrated complete disappearance of the ‘vasculitic’ changes without additional pathologic findings. Five months after therapy, the patient is without neurological symptoms and a PET-CT showed a complete remission. This case is a unique example of paraneoplastic central nervous system (CNS) involvement in a patient with newly diagnosed NLPHL. We present a review of the literature on paraneoplastic CNS symptoms in Hodgkin's lymphoma

Adaptation of antiretroviral therapy in human immunodeficiency virus infection with central nervous system involvement

The authors describe a patient with known human immunodeficiency virus (HIV)-1 infection who presented with two generalized seizures and was found to have extensive white matter disease and a left/bilateral temporo-occipital focal slowing on electroencephalography (EEG). There were no magnetic resonance imaging (MRI) or cerebrospinal fluid (CSF) indications for opportunistic infection. Plasma viremia was controlled, whereas viral replication was uncontrolled in CSF. CSF-specific genotype-guided adaptation of the antiretroviral therapy in order to optimize central nervous system (CNS) penetration resulted in clinical improvement and normalization of MRI and EEG. Our case report illustrates the importance of individualized antiretroviral therapy in HIV infected patients with neurological complication

Antimyelin antibodies in clinically isolated syndromes correlate with inflammation in MRI and CSF

Objective: We investigated the correlation of anti-myelin oligodendrocyte glycoprotein- (anti-MOG) and anti-myelin basic protein antibodies (anti-MBP) in serum of CIS patients with inflammatory signs in MRI and in CSF and, as previously suggested, the incidence of more frequent and rapid progression to clinically definite MS (CDMS). Methods: 133 CIS patients were analysed for anti-MOG and anti-MBP (Western blot). Routine CSF and cranial MRI (quantitatively and qualitatively) measures were analyzed. 55 patients had a follow-up of at least 12 months or until conversion to CDMS. Results: Patients with anti-MOG and anti-MBP had an increased intrathecal IgG production and CSF white blood cell count (p = 0.048 and p = 0.036). When anti-MBP alone, or both antibodies were present the cranial MRI showed significantly more T2 lesions (p = 0.007 and p = 0.01, respectively). There was a trend for more lesion dissemination in anti-MBP positive patients (p = 0.076). Conversely, anti-MOG- and/or anti-MBP failed to predict conversion to CDMS in our follow-up group (n = 55). Only in female patients with at least one MRI lesion (n = 34) did the presence of anti-MOG correlate with more frequent (p = 0.028) and more rapid (p = 0.0209) transition to CDMS. Conclusions: Presence of anti-MOG or anti-MBP or both was not significantly associated with conversion to CDMS in our CIS cohort. However, patients with anti-MOG and anti-MBP had higher lesion load and more disseminated lesions in cranial MRI as well as higher values for CSF leucocytes and intrathecal IgG production. Our data support a correlation of anti-MOG and anti-MBP to inflammatory signs in MRI and CSF. The prognostic value of these antibodies for CDMS, however, seems to be less pronounced than previously reporte

Regulatorische Expression des kostimulatorischen Moleküls ICOS in der Multiplen Sklerose

Costimulatory signals play a key role in regulating T cell activation and are believed to have decisive influence in the inciting and perpetuating cellular effector mechanisms in autoimmune diseases such as multiple sclerosis (MS). Inducible costimulator protein (ICOS), a recently identified member of the CD28-family, presumably affects the differentiation of Th1/Th2 cells after primary activation and modulates the immune response of effector/memory T cells. This study examined the constitutive expression as well as upregulated expression after antigen-specific stimulation of ICOS and the cytokines IL-4, IL- 10 and IFN-g in healthy donors and patients with MS. Gene-expression of these molecules and numerous B7-costimulatory molecules was also examined in brain tissue specimen from a patient with MS as well as in antigen presenting cells. Additionally ICOS expression in CD4+CD25+ cells and in Th1 and Th2 specific T cell lines was examined. For this purpose techniques such as flow cytometry and QRT-PCR were used. Furthermore the question whether QRTPCR is an appropriate approach to detect changes in the gene expression profile in low frequencies of autoreactive T cells was addressed. Analysis of ICOS gene-expression in Th1 and Th2 specific T cell lines clearly revealed ICOS gene expression being restricted to Th2 specific cells whereas it was absent in Th1 specific cell lines. Comparison of constitutive cell surface expression and upregulational kinetics of ICOS on CD4+- and CD8+-T cells showed no differences in patients with MS and healthy individuals. It was furthermore shown that ICOS is not exclusively expressed in CD4+CD25+ cells and thus is not a marker for this regulatory subset. Gene expression of ICOS, IL-4, IL-10 and IFN-g in PBMCs after antigen specific stimulation in MS patients and healthy individuals differed for IL-4 and IL-10 after stimulation with MBP84-99 and MOG, respectively. IL-4 expression was higher in healthy individuals, whereas greater IL-10 expression was detected in MS patients. However, as these two Th2 cytokines were upregulated in MS patients and healthy individuals in an opposing way, no conclusions with respect to their role and the role of ICOS in the pathogenesis of MS can be drawn. With regard to the expression of B7-costimulatory molecules in APC it is not surprising that the greatest amounts of gene expression was found in mature DC as these cells are the most potent APC. Some interesting findings could also be made for the gene-expression of ICOS and other costimulatory molecules in tissue specimen from a patient with MS: In one human brain specimen classified as “normal appearing white matter” upregulated gene expression of ICOS, other B7 costimulatory molecules and of inflammatory cytokines could be detected whereas in other specimen also classified as “normal appearing white matter” only moderate levels of these molecules could be found. This noteworthy observation indicates that in CNS of MS patients inflammatory activity is potentially present in histopathologically normal appearing areas. With regard to the applicability of QRT-PCR to detect changes in the gene expression profile of autoreactive T cells it was found that the method is useful as long as frequencies of the cells are higher as the elucidated detection threshold.Zur Aktivierung und Differenzierung von T Zellen sind zwei Signale erforderlich: Das antigenspezifische Signal das durch die Interaktion zwischen T-Zellrezeptor und dem MHC-Peptid-Komplex generiert wird (Signal 1) und die Aktivierung kostimulatorischer Moleküle (Signal 2). Die Kostimulation beeinflusst die Polarisierung der Immunantwort, die durch Unterschiede des Zytokinspektrums und der Effektoreigenschaften von T-Zellen gekennzeichnet ist. Man nimmt an, dass bei der Multiplen Sklerose (MS) unter anderem eine falsch regulierte Polarisation der Immunantwort in Richtung des Th1-Polarisationsmusters mit verändertem Zytokinspektrum zur Aktivierung autoreaktiver T-Zellen beiträgt. Somit ist das kürzlich identifizierte kostimulatorische Molekül ICOS aus der CD28-Familie, das die Differenzierung von Th1/Th2 Zellen nach deren primären Aktivierung beeinflusst und die Immunantwort von Effektor- und Gedächtnis T-Zellen moduliert, mutmaßlich in der Pathogenese der MS von Bedeutung. In der vorliegenden Arbeit wurde sowohl die konstitutive Genexpression als auch die Steigerung der Genexpression von ICOS und der Zytokine Interleukin-4, Interleukin-10 und Interferon- nach Antigen-spezifischer Stimulation in peripheren mononukleären Blutzellen von gesunden Probanden und von Patienten mit Multipler Sklerose untersucht. Die Genexpression dieser Moleküle und weiterer kostimulatorischer Moleküle der B7/CD28-Familie wurde weiterhin in Hirngewebeproben eines MS-Patienten und in Antigen-präsentierenden Zellen bestimmt. Zudem wurde die Oberflächenexpression von ICOS auf CD4+CD25high regulatorischen T-Zellen und die Genexpression von ICOS in Th1- und Th2-polarisierten T-Zellinien untersucht. ICOS wird präferenziell in Th2-polarisierten, jedoch nicht in Th1- polarisierten T-Zellinien exprimiert und CD4+CD25high regulatorische T-Zellen zeigen kein spezifisches ICOS-Expressionsmuster. Zwischen gesunden Probanden und MS-Patienten fanden sich keine Unterschiede der konstitutiven oder der induzierten Expression von ICOS auf CD4+ und CD8+ T-Zellen. Obwohl sich nach antigen-spezifischer Stimulation die Expression zweier Zytokine (Interleukin-4 und Interleukin-10) in jeweils einer von mehreren Stimulationsbedingungen zwischen MS-Patienten und gesunden Probanden unterschied, lassen sich daraus keine Rückschlüsse auf ihre Rolle bei der Entstehung von MS ziehen. Weiterhin fand sich eine hohe Genexpression der B7-Moleküle in professionellen Antigen-präsentierenden Zellen. In einigen als "normal erscheinende weiße Hirnsubstanz" deklarierten Hirngewebeproben eines MS-Patienten fand sich eine gesteigerte Genexpression von B7- und CD28-Molekülen. Mutmaßlich beschränken sich somit Entzündungsvorgänge in der MS nicht auf nach histopathologischen Kriterien verändertes Gewebe

Microfluidic cell culture

Microfluidic techniques allow precise control of fluids and particles at the nanoliter scale and facilitate simultaneous manipulation and analysis of cultured cells, starting from a single cell to larger populations and to intact tissues. The use of integrated microfluidic devices has considerably advanced the fields of quantitative and systems biology. In this review, we survey the recent developments in microfluidic cell culture, and discuss not only the advantages but also limitations of using such systems, and give an outlook on potential future developments

Fingolimod for multiple sclerosis : mechanism of action, clinical outcomes, and future directions

The oral sphingosine 1-phosphate receptor (S1PR) modulator fingolimod functionally antagonizes S1PR hereby blocking lymphocyte egress from secondary lymphoid organs to the peripheral blood circulation. This results in a reduction in peripheral lymphocyte counts, including potentially encephalitogenic T cells. In patients with relapsing multiple sclerosis fingolimod has been shown to be an effective treatment. In phase 2 and phase 3 studies fingolimod-treated patients had reduced disease activity clinically and in MRI. Although severe infectious complications occurred in single cases treated with fingolimod, the frequency of overall infections was comparable in fingolimod-treated patients and controls. Overall, in clinical studies fingolimod was well tolerated and had a favorable safety profile. In follow-up studies with continuous fingolimod, treatment showed sustained efficacy while being well tolerated